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Microglia and monocyte-derived macrophages: functionally distinct populations that act in concert in CNS plasticity and repair

Anat London, Merav Cohen, Michal Schwartz

Frontiers in Cellular Neuroscience · 2013

doi:10.3389/fncel.2013.00034

Abstract

Functional macrophage heterogeneity is recognized outside the central nervous system (CNS), where alternatively activated macrophages can perform immune-resolving functions. Such functional heterogeneity was largely ignored in the CNS, with respect to the resident microglia and the myeloid-derived cells recruited from the blood following injury or disease, previously defined as blood-derived microglia; both were indistinguishably perceived detrimental. Our studies have led us to view the myeloid-derived infiltrating cells as functionally distinct from the resident microglia, and accordingly, to name them monocyte-derived macrophages (mo-MΦ). Although microglia perform various maintenance and protective roles, under certain conditions when they can no longer provide protection, mo-MΦ are recruited to the damaged CNS; there, they act not as microglial replacements but rather assistant cells, providing activities that cannot be timely performed by the resident cells. Here, we focus on the functional heterogeneity of microglia/mo-MΦ, emphasizing that, as opposed to the mo-MΦ, microglia often fail to timely acquire the phenotype essential for CNS repair.

Full text

From PubMed Central, U.S. National Library of Medicine, as current on Oct 19, 2026. Paragraph numbers are ours, so an answer can point at one.

INTRODUCTION

Outside the central nervous system (CNS), macrophages are known to acquire distinct phenotypes, and accordingly, perform various different and even opposing functions. Macrophages are generally polarized into two major phenotypes: Th1-related cytokines, such as interferon-gamma (IFN-γ), and microbial challenge by products such as lipopolysaccharides (LPS) induce the classically activated M1 phenotype, driving macrophages toward a pro-inflammatory microbicidal function, whereas Th2 cytokines, such as interleukin-4 (IL-4) and IL-13 polarize macrophages to an alternatively activated M2 phenotype associated with wound healing and immune resolution. These different macrophage populations act following various insults outside the CNS where the CBR2+CX3BR1lowLy6Chigh subset, corresponding to the M1 phenotype, is the first recruited to the damage site and is typically pro-inflammatory, while the CBR2-CX3BR1highLy6Clow cells, matching the M2 phenotype, subsequently terminate the local inflammation as well as promoting regeneration and healing. These two polarized phenotypes are further classified, based on their diverse surface markers, phenotypes and functions, into a more continuum spectrum of macrophage repertoire.

In the CNS, however, such diversity of macrophage functions was largely overlooked, as microglia, the native immune cells of the CNS, were considered its exclusive innate components. Initially discovered by and his student, microglia are currently accepted as self-renewing cells with a unique embryonic origin, distributed along CNS parenchymal tissues. Their primary roles are the maintenance of normal CNS functions and the continuous search for alterations in homeostasis through their constantly scanning dynamic ramifications. Under pathological conditions, microglial functions are largely dependent on their activation stimuli; whereas moderate CNS damage evokes protection by microglia, intensive acute activation (for example in spinal cord injury, optic nerve crush, or stroke) and chronic activation, which characterizes neurodegenerative diseases, render these cells neurotoxic, potentially impairing neuronal activity. Such a phenotype not only prohibits microglia from resolving inflammatory damage but rather contributes to the vicious cycle of toxicity and calls for additional assistance to terminate the local inflammation.

As an immune privileged site, the CNS was, for decades, considered sealed for leukocyte entry, protected from the circulation behind the walls of the blood–brain barrier. Any recruitment of immune cells to the CNS was perceived as either a technical artifact or as part of the ongoing inflammatory damage. Further confusion resulted from the fact that blood-derived myeloid cells, recruited following CNS damage, were considered microglial reinforcements of comparable functions, and were accordingly termed “blood-derived microglia”. A series of recent innovative studies demonstrated that such infiltrating cells, which we defined as monocyte-derived macrophages (mo-MΦ), perform indispensable roles that cannot be provided by their resident counterparts. These studies challenged the traditional perception of macrophages in the CNS as a functionally homogeneous population. Moreover, they set the ground for a new era of research employing sophisticated techniques including parabiosis, head-protected bone marrow chimeras, transgenic mice, and fate mapping analysis, aimed at revealing the differential origin, phenotype, and function of distinct myeloid populations within the CNS. In this perspective, we will focus on the functional heterogeneity of microglia/mo-MΦ, addressing microglial functions as the first immunological support, the failure of these cells to provide significant protection under intensive acute or chronic activation, and the subsequent unique contribution of the mo-MΦ.

MICROGLIA IN MAINTENANCE AND DEFENSE

Similar to other tissue-resident macrophages outside the CNS, the primary role of microglia is to support normal tissue function, in this case neuronal integrity. The development of in vivo two-photon microscopy revolutionized our understanding of microglial functions under steady state. It allowed the study of non-activated microglia in intact brains of living animals. In these studies, using Cx3BR1GFP/+ or Iba1-EGFP transgenic mice, in which microglia are fluorescently labeled, these cells present highly motile processes, which directly contact astrocytes, neurons, and blood vessels, allowing the microglia to perform surveillance functions, constantly sensing subtle changes in their microenvironment. Microglia provide several housekeeping functions. For instance, these cells are involved in the maintenance of synapses; microglial ramifications directly interact with termini, spines, astrocytic processes, and synaptic clefts. These interactions enable the recognition of neuronal activity or structural alterations, according to which microglia facilitate synapse elimination, pruning or maturation, thereby preserve and organize neuronal networks. Microglia have been reported to support neurogenesis; they rapidly and efficiently clear out, by phagocytosis, the numerous apoptotic neural progenitor cells (NPCs) that do not incorporate into the circuitry, direct the migration and differentiation of NPCs, as well as secreting soluble factors promoting neurogenesis. Moreover, microglial activation following exercise and by local interaction with adaptive immune cells strongly supports neurogenesis and enhances cognitive functions. Additionally, several in vitro and in vivo studies demonstrated the capacity of microglia to secrete neurotrophic factors, e.g., nerve growth factor (NGF), neurotrophin-3 (NT-3), and NT-4. Under certain conditions microglia upregulate their brain-derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1) expression; both factors have protective and growth-promoting effects and are essential for learning and memory skills.

Being the native immune cells of the CNS, microglia act as the first line of defense, protecting the CNS from invading agents as well as internal enemies; microglia are involved in infection, inflammation, autoimmune disease, trauma, ischemia, and neurodegeneration. After initial exposure to a danger signal, microglia become activated; they upregulate expression levels of certain molecules such as CD11b and Iba1, and gain expression of molecules associated with antigen presentation, such as major histocompatibility complex (MHC)-II, B7.1, and B7.2 (CD80/86), which are absent in naïve microglia. Microglia then lose their ramified morphology and surveillance mode, and convert to amoeboid-like, functional cells.

Microglial functions under pathological conditions may reflect their diverse phenotypes acquired contingent to their activation signals. For example, activation of microglia by T cells that recognize CNS antigens or T cell-derived cytokines such as IFN-γ (at low concentrations) and IL-4 supports differentiation of NPCs and provides neuroprotection by regulating IGF-1 and tumor necrosis factor-alpha (TNF-α) levels. However, stimulation with LPS, amyloid-β or high concentrations of IFN-γ diminishes these effects. Moreover, activation of microglia by IL-4 prior to the LPS stimulation prevents the LPS-mediated-inhibition of the microglial neuroprotective effects. Thus, microglia are highly versatile cells; their regulated activation and proper termination might help in tissue preservation, repair, and renewal, while intensive acute or chronic activation may result in irreversible tissue loss.

Microglia exert several protective roles. These include removal by phagocytosis of pathogens and microbes, as well as clearance of toxic molecules, cell debris, remains of extracellular matrix, myelin derivatives, and protein deposits (e.g., amyloid-β or p-tau), all of which further contribute to the local inflammation and are inhibitory to regeneration and repair. Microglia can promote regeneration; other than removal of growth-inhibitory compounds, these cells produce classical growth factors required for remyelination and regeneration. Microglia were reported to support regeneration of the optic nerve as well as sensory axons in the injured spinal cord and to induce dopaminergic sprouting in the injured striatum. Additionally, microglia were shown to support neurogenesis and reduce neuronal death following stroke.

MICROGLIAL MALFUNCTION FOLLOWING INTENSIVE ACUTE OR CHRONIC ACTIVATION – A CALL FOR PERIPHERAL HELP

Substantial evident suggest that microglial activity is not always optimal and is often not sufficient to support significant CNS repair; on the contrary in many cases their insufficient support turns detrimental. Under intensive acute or chronic activation, microglia not only fail to provide the needed functions, but there are ample evidence implying that they can be actively deleterious; these cells secrete reactive oxygen species, nitric oxide (NO), and pro-inflammatory cytokines that can endanger neurons, oligodendrocytes, or essential structures of the extracellular matrix. Microglial malfunction was suggested as a possible etiology in schizophrenia, resulting in impaired pruning during neurodevelopment, disturbance of normal neurotransmitter function, and uncontrolled production of pro-inflammatory cytokines such as TNF and IL-6, as well as failure in clearance of neuronal corpses. Microglial abnormal response is also evident in Rett syndrome, a neurodevelopmental disease resulting from mutation of the gene encoding methyl-CpG binding protein (Mecp2). Mecp2-null microglia release glutamate at neurotoxic levels and have impaired phagocytic activity, possibly contributing to disease development. Impaired microglial function is also reported in amyotrophic lateral sclerosis (ALS), where microglia derived from mutant superoxide dismutase 1 (SOD1) mouse, an established disease model of ALS, induce more oxidative stress and cause higher neuronal loss compared with wt microglia. Interestingly, down regulation of the mutant levels in microglia results in reduced disease progression. In experimental autoimmune encephalomyelitis (EAE), a neurodegenerative disease model, microglial activation was inhibited by administration of ganciclovir to chimeric mice in which only the microglia express thymidine kinase that converts this drug into its cytotoxic form. Such specific microglial paralysis inhibits disease development and attenuates inflammatory CNS lesions. Moreover, in Alzheimer’s disease, characterization of fibrillar plaque development in brains of transgenic APP(SW) mice revealed that microglia are not only unable to clear amyloid-β deposits, but rather, contribute to plaque formation. Additionally, microglia-derived chronic inflammation was shown to precede neuronal loss in neonatal borna disease virus (BDV) infection.

Collectively, these evident suggest that under intensive acute or chronic activation microglia fail to acquire the desired phenotype, lose their essential functions and turn actively deleterious, and thus cannot provide immune resolution and subsequent CNS protection. In such scenarios, the recruitment of additional myeloid cells from the blood, comparable to microglia, is not likely. Rather, there is a need for peripheral intervention, in the form of unique cells, capable of providing the functions that cannot be delivered by the resident microglia.

FUNCTIONAL MACROPHAGE HETEROGENEITY

Indeed, intensive acute or chronic microglial activation drives these cells to produce a chemoattractive profile favoring the recruitment of monocytes and lymphocytes. However, as the CNS is an immune privileged site, it was assumed to exclude leukocyte trafficking. Consequently, several studies suggested that the recruitment of myeloid cells to the CNS reflected non-physiological entry, imposed by the unnatural experimental model. Other studies, although recognizing leukocyte entry to the CNS, interpreted their presence as a sign of pathology or malfunction that is detrimental and should be avoided. Moreover, the previous technical limited ability to distinguish between the infiltrating blood-derived cells and the resident microglia resulted in the view of the newly recruited cells as part of the microglial reservoir, leading to their inaccurate tagging as “blood-derived microglia”. This misleading nomenclature resulted in the erroneous perception of these cells as phenotypically and functionally comparable to microglia. Since then, advanced techniques have been developed to allow the blood-derived cells to be distinctly tracked and manipulated. A series of recent studies used head shielded [Cx3BR1GFP/+→WT] bone marrow chimeric mice, whose wt bone marrow was replaced with that of Cx3BR1GFP/+ mice. This approach allows the infiltrating myeloid cells, derived from donor bone marrow and labeled with GFP, to be distinguished from their resident counterparts, while avoiding any artifacts related to brain irradiation. These studies revealed the unique and non-redundant functions of the newly recruited cells and suggested the term “monocyte-derived macrophages (mo-MΦ)” to identify these cells as an entity separate from the resident microglia. mo-MΦ restrict amyloid-β plaques in a mouse model of Alzheimer’s disease, contribute to motor function recovery following spinal cord injury, promote survival of neurons and cell renewal in the injured retina, and were recently shown to arrest disease progression in Rett syndrome. These cells display immune-resolving characteristics and express anti-inflammatory cytokines, which are crucial for their neuroprotective function. Moreover, they restrict accumulation of other inflammatory leukocytes including neutrophils and resident microglia, mediate debris clearance by phagocytosis, and regulate the extracellular matrix and glial scar surrounding the damaged area. Importantly, inhibition or attenuation of the infiltration of mo-MΦ results in exacerbated damage, indicating that the resident microglia, which were spared in these experiments, cannot fulfill the protective functions provided by the mo-MΦ.

Additional reinforcement for the disparity of these two myeloid populations is the fact that resident microglia and mo-MΦ development is dependent on different transcription factors. While development of both microglia and mo-MΦ requires the transcription factor, Pu.1, the latter necessitates Myb and FLT3, whereas microglial development is csf1-receptor-dependent and FLT3- and Myb-independent. Each of these two myeloid populations has a unique set of transcription factors and regulators leading to a diverse pattern of gene expression. Advanced analysis methods compared the profile of gene expression, microRNAs (miRNAs) and transcription factors, of splenic Ly6Chi monocytes and CD39+ resident microglia in the SOD1 mouse, and of CD14+CD16- peripheral monocytes in ALS patients. In this study, microglial apoptosis was demonstrated along disease progression, while the macrophages derived from Ly6Chi monocytes proliferated in the spinal cord parenchyma and were associated with motor neuron loss. Notably, in this study, resident microglia were compared only to the inflammatory Ly6Chi mo-MΦ population, whereas a recent study reported the recruitment of two blood-derived macrophage populations following spinal cord injury: the Ly6ChiCX3BR1low pro-inflammatory and Ly6ClowCX3BR1hi anti-inflammatory cells, which acquire their phenotype via their trafficking route. Thus, it will be interesting to characterize the gene signature of both Ly6Chi and Ly6Clow mo-MΦ compared to resident microglia, and also to address the issue of where, how and when microglia acquire their phenotype.

All together, the evidence collected above indicates that under extensive inflammatory conditions, microglia lose their beneficial functions and instead display a deleterious role, further contributing to the spread of damage. Withstanding this vicious inflammatory cycle requires the recruitment of mo-MΦ, which induce resolution of the local immune response, rather than simply acting as microglial reinforcements. This perception leads, however, to the question of what drives the functional disparity between resident microglia and mo-MΦ. Specifically, what prevents microglia from acquiring the essential immune-resolving “alternatively activated” phenotype that is provided by the mo-MΦ? The answers to these questions may lie in the distinct origin of the two myeloid populations; microglial progenitors are yolk sac-derived macrophages that infiltrate the CNS during early embryogenesis, when bone marrow-derived hematopoiesis, from which mo-MΦ originate, is not yet established. Educated in the CNS from early ontogeny, microglia were never exposed to any other environment; they have a relatively long life-span and undergo moderate and limited turn-over by self-renewal of primitive myeloid precursors. In contrast, mo-MΦ are freshly recruited from the circulation. Their differences may also be related to the fact that microglia are the first to encounter the damaged tissue, which might dictate their phenotype, while the mo-MΦ, recruited at a slightly later stage, acquire their nature via their trafficking route to the CNS. Interestingly, such timely recruitment of myeloid subsets with differential functions is also evident in insults of non-CNS organs. Clearly, further research is needed in order to address these issues.

FUNCTIONAL RELATIONSHIPS BETWEEN THE MICROGLIA AND mo-MΦ – A CASCADE OF EVENTS

Based on the data reviewed above, we suggest here a cascade of events representing microglial functions within the CNS and the distinct contribution of mo-MΦ. Microglia enter the CNS during early developmental stages. By continuous scanning and sampling their environment via their dynamic processes, microglia are able to maintain CNS homeostasis; they preserve and modify (upon need) the synapse complex, support neurogenesis, secrete essential growth factors, and sustain normal CNS performance. Once encountering an unbalanced milieu, microglia become fully activated; retract their long ramifications, proliferate and shift toward a “ready to act” mode. Their subsequent function is very much dependent on their activation signal. A short and moderate stimulus will direct microglia to rapidly eliminate the source of damage without evoking a further immune response. Such stimuli are part of routine CNS maintenance and are generally resolved without activating or affecting other systems in the body. Even when the stimulus is stronger but short-lived, microglia can potentially cope with the danger signal, performing clearance of neurotoxic factors, supporting regeneration, and secreting neurotrophic factors supportive of remyelination. However, when the stimulus is intense or chronic, microglia can no longer handle the ongoing damage; these cells become neurotoxic and release reactive oxygen species, NO, proteases and pro-inflammatory cytokines, all of which endanger neuronal activity. Such microglial malfunction results in signals for recruitment of mo-MΦ to the damage site, which provide functions that cannot be delivered by the resident cells; mo-MΦ restrict the local inflammation, attenuate accumulation of misfolded proteins or any other intruders, restore homeostasis, and support healing and renewal. Unfortunately, the spontaneous response of mo-MΦ is often insufficient to achieve complete recovery. Thus, several therapeutic attempts to boost such a protective response by either direct administration of monocytes or indirectly augmenting their recruitment are currently underway (Figure 1).

LESSONS FROM OTHER TISSUE-SPECIFIC RESIDENT MACROPHAGES

Although unique, microglia are not the sole tissue-specific resident myeloid-derived cells. Many organs in the body contain distinctive resident macrophages whose properties are tailored to the host tissue (Figure 2). Langerhans cells (LCs), for example, are the resident myeloid cells of the epidermis. Similar to microglia, they have extended dendritic processes that embrace neighboring keratinocytes and scan the epidermis for pathogens and toxic molecules. These cells are endowed with the C-type lectin, Langerin, used for interaction with bacteria, fungi, and viruses. Like microglia, LCs descend from embryonic precursors, possibly yolk sac macrophages or fetal liver monocytes, and are renewed independently of the bone marrow, by in situ proliferation upon need. Moreover, as in microglial activation, upon capture of pathogens, LCs undergo phenotypic changes including increased expression of MHC-I and -II, and of the co-stimulatory molecules CD80, CD86, and CD40. However, unlike microglia, which are restricted to the CNS parenchyma, LCs upregulate the lymph node-homing receptor, CCR7, which eventually leads to their migration to peripheral lymph nodes where they induce a specific adaptive immune response against skin invading pathogens. Intestinal macrophages are the largest population of mononuclear phagocytes in the body. Similar to microglia, they have essential functions under both normal and pathological conditions; intestinal macrophages preserve a delicate equilibrium between commensal bacteria and the host, maintaining epithelial integrity and mucosal homeostasis. These cells act as the first line of defense protecting the highly exposed mucosa from harmful pathogens, removing dead cells and debris, and modulating the local inflammatory response. Unlike other tissue macrophages, upon activation, for instance by certain Toll-like receptor (TLR) ligands, intestinal macrophages do not express high levels of co-stimulatory molecules nor do they secrete pro-inflammatory cytokines. Rather, they produce anti-inflammatory mediators such as IL-10 and prostaglandin E2 that restrict the local immune response. Unlike microglia, the replenishment of intestinal macrophages is mostly associated with the recruitment of circulating monocytes. However, the possibility of self-renewal under steady state has also been raised. Kupffer cells are the macrophages of the liver. These cells are mainly involved in clearance of pathogens and host-derived waste; they are constantly exposed to bacterial endotoxin (LPS) and microbial debris delivered from the gastrointestinal tract and are involved in removal of senescent or malformed red blood cells and phagocytosis of soluble immunoglobulin G (IgG) complexes, microorganisms and eukaryotic cells. In addition to their role as phagocytes, Kupffer cells act as effective antigen presenting cells; upon Hepatitis C virus infection, human Kupffer cells elevate MHC-I and -II expression, upregulate co-stimulatory molecules, and interact with T cells. However, several studies also demonstrated the immune-resolving nature of Kupffer cells, which were shown to suppress lymphocytes in culture, secrete IL-10 in response to LPS challenge and facilitate Fas ligand (FasL)-mediated apoptosis of T cells in a liver transplant model. Thus, similarly to CNS heterogeneous macrophages, Kupffer cells seem to perform highly versatile functions. These cells, like microglia and LCs appear to self-renew independently of bone marrow-derived precursors. However, a study addressing Kupffer cell heterogeneity identified two subsets of Kupffer cells; one of them is radiosensitive and rapidly replaced from hematogenous precursors, indicating that the issue of Kupffer cell renewal is still unresolved.

CONCLUSIONS AND FUTURE DIRECTIONS

The evidence collected in this perspective supports the concept of functional macrophage heterogeneity within the CNS. Due to their similar morphology, previously assumed shared origin and subsequent misleading nomenclature, as well as the lack of available techniques to distinguish between the two populations, microglia and mo-MΦ were erroneously assumed to comprise a single population. Alternatively, and based on the ample findings addressed above, our model suggests that when it comes to CNS macrophages initial impressions can be deceiving; although they appear similar, mo-MΦ and microglia present different gene expression patterns and phenotypes, and are functionally distinct. Additional research is needed in order to further reveal the different function of these two distinct populations and the conditions that determine their unique phenotype. Such research will help resolving the misunderstanding that resulted from the previously held blanket view of these cells as homogeneously destructive, and might assist in employing specific manipulations of the two subsets as a potential therapeutic approach.

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

References 138

  1. 1.

    Aarum J. Sandberg K. Haeberlein S. L. Persson M. A. (2003 ). Migration and differentiation of neural precursor cells can be directed by microglia. Proc. Natl. Acad. Sci. U.S.A. 100 15983–15988

    Not in our library10.1073/pnas.2237050100

  2. 2.

    Ajami B. Bennett J. L. Krieger C. Mcnagny K. M. Rossi F. M. (2011 ). Infiltrating monocytes trigger EAE progression, but do not contribute to the resident microglia pool. Nat. Neurosci. 14 1142–1149

    Not in our library10.1038/nn.2887

  3. 3.

    Ajami B. Bennett J. L. Krieger C. Tetzlaff W. Rossi F. M. (2007 ). Local self-renewal can sustain CNS microglia maintenance and function throughout adult life. Nat. Neurosci. 10 1538–1543

    Not in our library10.1038/nn2014

  4. 4.

    Arnold L. Henry A. Poron F. Baba-Amer Y. Van Rooijen N. Plonquet, A., et al. (2007 ). Inflammatory monocytes recruited after skeletal muscle injury switch into antiinflammatory macrophages to support myogenesis. J. Exp. Med. 204 1057–1069

    Not in our library10.1084/jem.20070075

  5. 5.

    Auffray C. Sieweke M. H. Geissmann F. (2009 ). Blood monocytes: development, heterogeneity, and relationship with dendritic cells. Annu. Rev. Immunol. 27 669–692

    Not in our library10.1146/annurev.immunol.021908.132557

  6. 6.

    Avidan H. Kipnis J. Butovsky O. Caspi R. R. Schwartz M. (2004 ). Vaccination with autoantigen protects against aggregated beta-amyloid and glutamate toxicity by controlling microglia: effect of CD4+CD25+ T cells. Eur. J. Immunol. 34 3434–3445

    Not in our library10.1002/eji.200424883

  7. 7.

    Batchelor P. E. Liberatore G. T. Wong J. Y. Porritt M. J. Frerichs F. Donnan G. A. et al. (1999 ). Activated macrophages and microglia induce dopaminergic sprouting in the injured striatum and express brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor. J. Neurosci. 19 1708–1716

    Not in our library10.1523/jneurosci.19-05-01708.1999

  8. 8.

    Bechmann I. Goldmann J. Kovac A. D. Kwidzinski E. Simburger E. Naftolin F. et al. (2005 ). Circulating monocytic cells infiltrate layers of anterograde axonal degeneration where they transform into microglia. FASEB J. 19 647–649

    Not in our library10.1096/fj.04-2599fje

  9. 9.

    Beers D. R. Henkel J. S. Xiao Q. Zhao W. Wang J. Yen A. A. et al. (2006 ). Wild-type microglia extend survival in PU.1 knockout mice with familial amyotrophic lateral sclerosis. Proc. Natl. Acad. Sci. U.S.A. 103 16021–16026

    Not in our library10.1073/pnas.0607423103

  10. 10.

    Bilzer M. Roggel F. Gerbes A. L. (2006 ). Role of Kupffer cells in host defense and liver disease. Liver Int. 26 1175–1186

    Not in our library10.1111/j.1478-3231.2006.01342.x

  11. 11.

    Block M. L. Hong J. S. (2005 ). Microglia and inflammation-mediated neurodegeneration: multiple triggers with a common mechanism. Prog. Neurobiol. 76 77–98

    Not in our library10.1016/j.pneurobio.2005.06.004

  12. 12.

    Block M. L. Zecca L. Hong J. S. (2007 ). Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nat. Rev. Neurosci. 8 57–69

    Not in our library10.1038/nrn2038

  13. 13.

    Boillée, S. Yamanaka K. Lobsiger C. S. Copeland N. G. Jenkins N. A. Kassiotis G. et al. (2006 ). Onset and progression in inherited ALS determined by motor neurons and microglia. Science 2 1389–1392

    Not in our library10.1126/science.1123511

  14. 14.

    Boster A. Edan G. Frohman E. Javed A. Stuve O. Tselis A. et al. (2008 ). Intense immunosuppression in patients with rapidly worsening multiple sclerosis: treatment guidelines for the clinician. Lancet Neurol. 7 173–183

    Not in our library10.1016/s1474-4422(08)70020-6

  15. 15.

    Burgio V. L. Ballardini G. Artini M. Caratozzolo M. Bianchi F. B. Levrero M. (1998 ). Expression of co-stimulatory molecules by Kupffer cells in chronic hepatitis of hepatitis C virus etiology. Hepatology 27 1600–1606

    Not in our library10.1002/hep.510270620

  16. 16.

    Butovsky O. Hauben E. Schwartz M. (2001 ). Morphological aspects of spinal cord autoimmune neuroprotection: colocalization of T cells with B7–2 (CD86) and prevention of cyst formation. FASEB J. 15 1065–1067

    Not in our library10.1096/fj.00-0550fje

  17. 17.

    Butovsky O. Koronyo-Hamaoui M. Kunis G. Ophir E. Landa G. Cohen H. et al. (2006a ). Glatiramer acetate fights against Alzheimer’s disease by inducing dendritic-like microglia expressing insulin-like growth factor 1. Proc. Natl. Acad. Sci. U.S.A. 103 11784–11789

    Not in our library10.1073/pnas.0604681103

  18. 18.

    Butovsky O. Landa G. Kunis G. Ziv Y. Avidan H. Greenberg N. et al. (2006b ). Induction and blockage of oligodendrogenesis by differently activated microglia in an animal model of multiple sclerosis. J. Clin. Invest. 116 905–915

    Not in our library10.1172/jci26836

  19. 19.

    Butovsky O. Ziv Y. Schwartz A. Landa G. Talpalar A. E. Pluchino S. et al. (2006c ). Microglia activated by IL-4 or IFN-gamma differentially induce neurogenesis and oligodendrogenesis from adult stem/progenitor cells. Mol. Cell. Neurosci. 31 149–160

    Not in our library10.1016/j.mcn.2005.10.006

  20. 20.

    Butovsky O. Kunis G. Koronyo-Hamaoui M. Schwartz M. (2007 ). Selective ablation of bone marrow-derived dendritic cells increases amyloid plaques in a mouse Alzheimer’s disease model. Eur. J. Neurosci. 26 413–416

    Not in our library10.1111/j.1460-9568.2007.05652.x

  21. 21.

    Butovsky O. Siddiqui S. Gabriely G. Lanser A. J. Dake B. Murugaiyan G. et al. (2012 ). Modulating inflammatory monocytes with a unique microRNA gene signature ameliorates murine ALS. J. Clin. Invest. 122 3063–3087

    Not in our library10.1172/jci62636

  22. 22.

    Butovsky O. Talpalar A. E. Ben-Yaakov K. Schwartz M. (2005 ). Activation of microglia by aggregated beta-amyloid or lipopolysaccharide impairs MHC-II expression and renders them cytotoxic whereas IFN-gamma and IL-4 render them protective. Mol. Cell. Neurosci. 29 381–393

    Not in our library10.1016/j.mcn.2005.03.005

  23. 23.

    Cajal S. R. (1913 ). Contribución al conocimiento de la neuroglia del cerebro humano. Trab. Lab. Invest. Biol. 11 255–345

    Not in our library

  24. 24.

    Callery M. P. Mangino M. J. Flye M. W. (1991 ). Arginine-specific suppression of mixed lymphocyte culture reactivity by Kupffer cells – a basis of portal venous tolerance. Transplantation 51 1076–1080

    Not in our library10.1097/00007890-199105000-00028

  25. 25.

    Carson M. J. Bilousova T. V. Puntambekar S. S. Melchior B. Doose J. M. Ethell I. M. (2007 ). A rose by any other name? The potential consequences of microglial heterogeneity during CNS health and disease. Neurotherapeutics 4 571–579

    Not in our library10.1016/j.nurt.2007.07.002

  26. 26.

    Centonze D. Muzio L. Rossi S. Cavasinni F. De Chiara V. Bergami A. et al. (2009 ). Inflammation triggers synaptic alteration and degeneration in experimental autoimmune encephalomyelitis. J. Neurosci. 29 3442–3452

    Not in our library10.1523/jneurosci.5804-08.2009

  27. 27.

    Choi S. H. Veeraraghavalu K. Lazarov O. Marler S. Ransohoff R. M. Ramirez J. M. et al. (2008 ). Non-cell-autonomous effects of presenilin 1 variants on enrichment-mediated hippocampal progenitor cell proliferation and differentiation. Neuron 59 568–580

    Not in our library10.1016/j.neuron.2008.07.033

  28. 28.

    Chorro L. Geissmann F. (2010 ). Development and homeostasis of ‘resident’ myeloid cells: the case of the Langerhans cell. Trends Immunol. 31 438–445

    Not in our library10.1016/j.it.2010.09.003

  29. 29.

    Chorro L. Sarde A. Li M. Woollard K. J. Chambon P. Malissen B. et al. (2009 ). Langerhans cell (LC) proliferation mediates neonatal development, homeostasis, and inflammation-associated expansion of the epidermal LC network. J. Exp. Med. 206 3089–3100

    Not in our library10.1084/jem.20091586

  30. 30.

    Chung H. Brazil M. I. Soe T. T. Maxfield F. R. (1999 ). Uptake, degradation, and release of fibrillar and soluble forms of Alzheimer’s amyloid beta-peptide by microglial cells. J. Biol. Chem. 274 32301–32308

    Not in our library10.1074/jbc.274.45.32301

  31. 31.

    Colton C. A. (2013 ). Immune heterogeneity in neuroinflammation: dendritic cells in the brain. J. Neuroimmune Pharmacol. 8 145–162

    Not in our library10.1007/s11481-012-9414-8

  32. 32.

    Davalos D. Grutzendler J. Yang G. Kim J. V. Zuo Y. Jung S. et al. (2005 ). ATP mediates rapid microglial response to local brain injury in vivo. Nat. Neurosci. 8 752–758

    Not in our library10.1038/nn1472

  33. 33.

    de Jong M. A. Geijtenbeek T. B. (2010 ). Langerhans cells in innate defense against pathogens. Trends Immunol. 31 452–459

    Not in our library10.1016/j.it.2010.08.002

  34. 34.

    Del Rio-Hortega P. (1919 ). El tercer elemento de los centros nerviosos I La microglia en estado normal II Intervencïon de la microglia en los procesos patológicos III Naturaleza probable de la microglia. Bol. de la Soc. Esp. de Biol. 9 69–120

    Not in our library

  35. 35.

    Derecki N. C. Cronk J. C. Kipnis J. (2013 ). The role of microglia in brain maintenance: implications for Rett syndrome. Trends Immunol. 34 144–150

    Not in our library10.1016/j.it.2012.10.002

  36. 36.

    Derecki N. C. Cronk J. C. Lu Z. Xu E. Abbott S. B. Guyenet P. G. et al. (2012 ). Wild-type microglia arrest pathology in a mouse model of Rett syndrome. Nature 484 105–109

    Not in our library10.1038/nature10907

  37. 37.

    de Witte L. Nabatov A. Pion M. Fluitsma D. De Jong M. A. De Gruijl T. et al. (2007 ). Langerin is a natural barrier to HIV-1 transmission by Langerhans cells. Nat. Med. 13 367–371

    Not in our library10.1038/nm1541

  38. 38.
    Hematopoietic cells differentiate into both microglia and macroglia in the brains of adult mice · 1997
    Not checked
  39. 39.

    Ekdahl C. T. Claasen J. H. Bonde S. Kokaia Z. Lindvall O. (2003 ). Inflammation is detrimental for neurogenesis in adult brain. Proc. Natl. Acad. Sci. U.S.A. 100 13632–13637

    Not in our library10.1073/pnas.2234031100

  40. 40.

    Elkabes S. Dicicco-Bloom E. M. Black I. B. (1996 ). Brain microglia/macrophages express neurotrophins that selectively regulate microglial proliferation and function. J. Neurosci. 16 2508–2521

    Not in our library10.1523/jneurosci.16-08-02508.1996

  41. 41.

    Ginhoux F. Greter M. Leboeuf M. Nandi S. See P. Gokhan S. et al. (2010 ). Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science 330 841–845

    Not in our library10.1126/science.1194637

  42. 42.

    Gomez Perdiguero E. Schulz C. Geissmann F. (2013 ). Development and homeostasis of “resident” myeloid cells: the case of the microglia. Glia 61 112–120

    Not in our library10.1002/glia.22393

  43. 43.

    Gordon S. (2003 ). Alternative activation of macrophages. Nat. Rev. Immunol. 3 23–35

    Not in our library10.1038/nri978

  44. 44.

    Gordon S. Martinez F. O. (2010 ). Alternative activation of macrophages: mechanism and functions. Immunity 32 593–604

    Not in our library10.1016/j.immuni.2010.05.007

  45. 45.

    Gordon S. Taylor P. R. (2005 ). Monocyte and macrophage heterogeneity. Nat. Rev. Immunol. 5 953–964

    Not in our library10.1038/nri1733

  46. 46.

    Gris D. Marsh D. R. Oatway M. A. Chen Y. Hamilton E. F. Dekaban G. A. et al. (2004 ). Transient blockade of the CD11d/CD18 integrin reduces secondary damage after spinal cord injury, improving sensory, autonomic, and motor function. J. Neurosci. 24 4043–4051

    Not in our library10.1523/jneurosci.5343-03.2004

  47. 47.

    Hanisch U. K. Kettenmann H. (2007 ). Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat. Neurosci. 10 1387–1394

    Not in our library10.1038/nn1997

  48. 48.

    Hausler K. G. Prinz M. Nolte C. Weber J. R. Schumann R. R. Kettenmann H. et al. (2002 ). Interferon-gamma differentially modulates the release of cytokines and chemokines in lipopolysaccharide- and pneumococcal cell wall-stimulated mouse microglia and macrophages. Eur. J. Neurosci. 16 2113–2122

    Not in our library10.1046/j.1460-9568.2002.02287.x

  49. 49.

    Heppner F. L. Greter M. Marino D. Falsig J. Raivich G. Hovelmeyer N. et al. (2005 ). Experimental autoimmune encephalomyelitis repressed by microglial paralysis. Nat. Med. 11 146–152

    Not in our library10.1038/nm1177

  50. 50.

    Hirasawa T. Ohsawa K. Imai Y. Ondo Y. Akazawa C. Uchino S. et al. (2005 ). Visualization of microglia in living tissues using Iba1-EGFP transgenic mice. J. Neurosci. Res. 81 357–362

    Not in our library10.1002/jnr.20480

  51. 51.

    Hirotani T. Lee P. Y. Kuwata H. Yamamoto M. Matsumoto M. Kawase I. et al. (2005 ). The nuclear IkappaB protein IkappaBNS selectively inhibits lipopolysaccharide-induced IL-6 production in macrophages of the colonic lamina propria. J. Immunol. 174 3650–3657

    Not in our library10.4049/jimmunol.174.6.3650

  52. 52.

    Hoeffel G. Wang Y. Greter M. See P. Teo P. Malleret B. et al. (2012 ). Adult Langerhans cells derive predominantly from embryonic fetal liver monocytes with a minor contribution of yolk sac-derived macrophages. J. Exp. Med. 209 1167–1181

    Not in our library10.1084/jem.20120340

  53. 53.

    Hsieh J. Aimone J. B. Kaspar B. K. Kuwabara T. Nakashima K. Gage F. H. (2004 ). IGF-I instructs multipotent adult neural progenitor cells to become oligodendrocytes. J. Cell Biol. 164 111–122

    Not in our library10.1083/jcb.200308101

  54. 54.

    Jung S. Aliberti J. Graemmel P. Sunshine M. J. Kreutzberg G. W. Sher A. et al. (2000 ). Analysis of fractalkine receptor CX(3)BR1 function by targeted deletion and green fluorescent protein reporter gene insertion. Mol. Cell. Biol. 20 4106–4114

    Not in our library10.1128/mcb.20.11.4106-4114.2000

  55. 55.

    Kettenmann H. Hanisch U. K. Noda M. Verkhratsky A. (2011 ). Physiology of microglia. Physiol. Rev. 91 461–553

    Not in our library10.1152/physrev.00011.2010

  56. 56.

    Klein I. Cornejo J. C. Polakos N. K. John B. Wuensch S. A. Topham D. J. et al. (2007 ). Kupffer cell heterogeneity: functional properties of bone marrow derived and sessile hepatic macrophages. Blood 110 4077–4085

    Not in our library10.1182/blood-2007-02-073841

  57. 57.

    Knolle P. Schlaak J. Uhrig A. Kempf P. Meyer Zum Buschenfelde K. H. Gerken G. (1995 ). Human Kupffer cells secrete IL-10 in response to lipopolysaccharide (LPS) challenge. J. Hepatol. 22 226–229

    Not in our library10.1016/0168-8278(95)80433-1

  58. 58.

    Kotter M. R. Setzu A. Sim F. J. Van Rooijen N. Franklin R. J. (2001 ). Macrophage depletion impairs oligodendrocyte remyelination following lysolecithin-induced demyelination. Glia 35 204–212

    Not in our library10.1002/glia.1085

  59. 59.

    Langerhans P. (1868 ). über die Nerven der menschlichen Haut. Virchows Arch. 44 325–337

    Not in our library

  60. 60.

    Lee J. L. Everitt B. J. Thomas K. L. (2004 ). Independent cellular processes for hippocampal memory consolidation and reconsolidation. Science 304 839–843

    Not in our library10.1126/science.1095760

  61. 61.

    Liu Y. Hao W. Letiembre M. Walter S. Kulanga M. Neumann H. et al. (2006 ). Suppression of microglial inflammatory activity by myelin phagocytosis: role of p47-PHOX-mediated generation of reactive oxygen species. J. Neurosci. 26 12904–12913

    Not in our library10.1523/jneurosci.2531-06.2006

  62. 62.

    London A. Itskovich E. Benhar I. Kalchenko V. Mack M. Jung S. et al. (2011 ). Neuroprotection and progenitor cell renewal in the injured adult murine retina requires healing monocyte-derived macrophages. J. Exp. Med. 208 23–39

    Not in our library10.1084/jem.20101202

  63. 63.

    Maezawa I. Jin L. W. (2010 ). Rett syndrome microglia damage dendrites and synapses by the elevated release of glutamate. J. Neurosci. 30 5346–5356

    Not in our library10.1523/jneurosci.5966-09.2010

  64. 64.

    Magnus T. Chan A. Grauer O. Toyka K. V. Gold R. (2001 ). Microglial phagocytosis of apoptotic inflammatory T cells leads to down-regulation of microglial immune activation. J. Immunol. 167 5004–5010

    Not in our library10.4049/jimmunol.167.9.5004

  65. 65.

    Majumdar A. Cruz D. Asamoah N. Buxbaum A. Sohar I. Lobel P. et al. (2007 ). Activation of microglia acidifies lysosomes and leads to degradation of Alzheimer amyloid fibrils. Mol. Biol. Cell 18 1490–1496

    Not in our library10.1091/mbc.e06-10-0975

  66. 66.

    Mantovani A. Sica A. Locati M. (2005 ). Macrophage polarization comes of age. Immunity 23 344–346

    Not in our library10.1016/j.immuni.2005.10.001

  67. 67.

    Martinez F. O. Helming L. Gordon S. (2009 ). Alternative activation of macrophages: an immunologic functional perspective. Annu. Rev. Immunol. 27 451–483

    Not in our library10.1146/annurev.immunol.021908.132532

  68. 68.

    McGeer P. L. McGeer E. Rogers J. Sibley J. (1990 ). Anti-inflammatory drugs and Alzheimer disease. Lancet 335 1037

    Not in our library10.1016/0140-6736(90)91101-f

  69. 69.

    McKercher S. R. Torbett B. E. Anderson K. L. Henkel G. W. Vestal D. J. Baribault H. et al. (1996 ). Targeted disruption of the PU.1 gene results in multiple hematopoietic abnormalities. EMBO J. 15 5647–5658

    Not in our library

  70. 70.

    Merad M. Ginhoux F. Collin M. (2008 ). Origin, homeostasis and function of Langerhans cells and other langerin-expressing dendritic cells. Nat. Rev. Immunol. 8 935–947

    Not in our library10.1038/nri2455

  71. 71.

    Merad M. Manz M. G. Karsunky H. Wagers A. Peters W. Charo I. et al. (2002 ). Langerhans cells renew in the skin throughout life under steady-state conditions. Nat. Immunol. 3 1135–1141

    Not in our library10.1038/ni852

  72. 72.

    Mildner A. Schlevogt B. Kierdorf K. Bottcher C. Erny D. Kummer M. P. et al. (2011 ). Distinct and non-redundant roles of microglia and myeloid subsets in mouse models of Alzheimer’s disease. J. Neurosci. 31 11159–11171

    Not in our library10.1523/jneurosci.6209-10.2011

  73. 73.

    Mildner A. Schmidt H. Nitsche M. Merkler D. Hanisch U. K. Mack M. et al. (2007 ). Microglia in the adult brain arise from Ly-6ChiCBR2+ monocytes only under defined host conditions. Nat. Neurosci. 10 1544–1553

    Not in our library10.1038/nn2015

  74. 74.

    Miyagawa-Hayashino A. Tsuruyama T. Egawa H. Haga H. Sakashita H. Okuno T. et al. (2007 ). FasL expression in hepatic antigen-presenting cells and phagocytosis of apoptotic T cells by FasL+ Kupffer cells are indicators of rejection activity in human liver allografts. Am. J. Pathol. 171 1499–1508

    Not in our library10.2353/ajpath.2007.070027

  75. 75.

    Mizuno M. Yamada K. Olariu A. Nawa H. Nabeshima T. (2000 ). Involvement of brain-derived neurotrophic factor in spatial memory formation and maintenance in a radial arm maze test in rats. J. Neurosci. 20 7116–7121

    Not in our library10.1523/jneurosci.20-18-07116.2000

  76. 76.

    Monje M. L. Toda H. Palmer T. D. (2003 ). Inflammatory blockade restores adult hippocampal neurogenesis. Science 302 1760–1765

    Not in our library10.1126/science.1088417

  77. 77.

    Mosser D. M. Edwards J. P. (2008 ). Exploring the full spectrum of macrophage activation. Nat. Rev. Immunol. 8 958–969

    Not in our library10.1038/nri2448

  78. 78.

    Mowat A. M. Bain C. C. (2011 ). Mucosal macrophages in intestinal homeostasis and inflammation. J. Innate Immun. 3 550–564

    Not in our library10.1159/000329099

  79. 79.

    Munn N. A. (2000 ). Microglia dysfunction in schizophrenia: an integrative theory. Med. Hypotheses 54 198–202

    Not in our library10.1054/mehy.1999.0018

  80. 80.

    Murabe Y. Sano Y. (1982 ). Morphological studies on neuroglia. V. Microglial cells in the cerebral cortex of the rat, with special reference to their possible involvement in synaptic function. Cell Tissue Res. 223 493–506

    Not in our library10.1007/bf00218471

  81. 81.

    Muzio L. Martino G. Furlan R. (2007 ). Multifaceted aspects of inflammation in multiple sclerosis: the role of microglia. J. Neuroimmunol. 191 39–44

    Not in our library10.1016/j.jneuroim.2007.09.016

  82. 82.

    Nahrendorf M. Swirski F. K. Aikawa E. Stangenberg L. Wurdinger T. Figueiredo J. L. et al. (2007 ). The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions. J. Exp. Med. 204 3037–3047

    Not in our library10.1084/jem.20070885

  83. 83.

    Naito M. Hasegawa G. Ebe Y. Yamamoto T. (2004 ). Differentiation and function of Kupffer cells. Med. Electron Microsc. 37 16–28

    Not in our library10.1007/s00795-003-0228-x

  84. 84.

    Nakajima K. Honda S. Tohyama Y. Imai Y. Kohsaka S. Kurihara T. (2001 ). Neurotrophin secretion from cultured microglia. J. Neurosci. Res. 65 322–331

    Not in our library10.1002/jnr.1157

  85. 85.

    Neumann J. Gunzer M. Gutzeit H. O. Ullrich O. Reymann K. G. Dinkel K. (2006 ). Microglia provide neuroprotection after ischemia. FASEB J. 20 714–716

    Not in our library10.1096/fj.05-4882fje

  86. 86.

    Neumann J. Sauerzweig S. Ronicke R. Gunzer F. Dinkel K. Ullrich O. et al. (2008 ). Microglia cells protect neurons by direct engulfment of invading neutrophil granulocytes: a new mechanism of CNS immune privilege. J. Neurosci. 28 5965–5975

    Not in our library10.1523/jneurosci.0060-08.2008

  87. 87.

    Nimmerjahn A. Kirchhoff F. Helmchen F. (2005 ). Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 308 1314–1318

    Not in our library10.1126/science.1110647

  88. 88.

    Okamura T. Katayama T. Obinata C. Iso Y. Chiba Y. Kobayashi H. et al. (2012 ). Neuronal injury induces microglial production of macrophage inflammatory protein-1alpha in rat corticostriatal slice cultures. J. Neurosci. Res. 90 2127–2133

    Not in our library10.1002/jnr.23105

  89. 89.

    Ovanesov M. V. Moldovan K. Smith K. Vogel M. W. Pletnikov M. V. (2008 ). Persistent Borna Disease Virus (BDV) infection activates microglia prior to a detectable loss of granule cells in the hippocampus. J. Neuroinflammation 5 16

    Not in our library10.1186/1742-2094-5-16

  90. 90.

    Paolicelli R. C. Bolasco G. Pagani F. Maggi L. Scianni M. Panzanelli P. et al. (2011 ). Synaptic pruning by microglia is necessary for normal brain development. Science 333 1456–1458

    Not in our library10.1126/science.1202529

  91. 91.

    Parker G. A. Picut C. A. (2012 ). Immune functioning in non lymphoid organs: the liver. Toxicol. Pathol. 40 237–247

    Not in our library10.1177/0192623311428475

  92. 92.

    Perry V. H. Nicoll J. A. Holmes C. (2010 ). Microglia in neurodegenerative disease. Nat. Rev. Neurol. 6 193–201

    Not in our library10.1038/nrneurol.2010.17

  93. 93.

    Popovich P. G. Guan Z. Wei P. Huitinga I. Van Rooijen N. Stokes B. T. (1999 ). Depletion of hematogenous macrophages promotes partial hindlimb recovery and neuroanatomical repair after experimental spinal cord injury. Exp. Neurol. 158 351–365

    Not in our library10.1006/exnr.1999.7118

  94. 94.

    Popovich P. G. Hickey W. F. (2001 ). Bone marrow chimeric rats reveal the unique distribution of resident and recruited macrophages in the contused rat spinal cord. J. Neuropathol. Exp. Neurol. 60 676–685

    Not in our library10.1093/jnen/60.7.676

  95. 95.

    Prewitt C. M. Niesman I. R. Kane C. J. Houle J. D. (1997 ). Activated macrophage/microglial cells can promote the regeneration of sensory axons into the injured spinal cord. Exp. Neurol. 148 433–443

    Not in our library10.1006/exnr.1997.6694

  96. 96.

    Priller J. Flugel A. Wehner T. Boentert M. Haas C. A. Prinz M. et al. (2001 ). Targeting gene-modified hematopoietic cells to the central nervous system: use of green fluorescent protein uncovers microglial engraftment. Nat. Med. 7 1356–1361

    Not in our library10.1038/nm1201-1356

  97. 97.

    Prinz M. Priller J. Sisodia S. S. Ransohoff R. M. (2011 ). Heterogeneity of CNS myeloid cells and their roles in neurodegeneration. Nat. Neurosci. 14 1227–1235

    Not in our library10.1038/nn.2923

  98. 98.

    Rabchevsky A. G. Streit W. J. (1997 ). Grafting of cultured microglial cells into the lesioned spinal cord of adult rats enhances neurite outgrowth. J. Neurosci. Res. 47 34–48

    Not in our library

  99. 99.

    Ransohoff R. M. Engelhardt B. (2012 ). The anatomical and cellular basis of immune surveillance in the central nervous system. Nat. Rev. Immunol. 12 623–635

    Not in our library10.1038/nri3265

  100. 100.

    Ransohoff R. M. Perry V. H. (2009 ). Microglial physiology: unique stimuli, specialized responses. Annu. Rev. Immunol. 27 119–145

    Not in our library10.1146/annurev.immunol.021908.132528

  101. 101.

    Ravichandran K. S. (2003 ). “Recruitment signals” from apoptotic cells: invitation to a quiet meal. Cell 113 817–820

    Not in our library10.1016/s0092-8674(03)00471-9

  102. 102.

    Rogler G. Hausmann M. Vogl D. Aschenbrenner E. Andus T. Falk W. et al. (1998 ). Isolation and phenotypic characterization of colonic macrophages. Clin. Exp. Immunol. 112 205–215

    Not in our library10.1046/j.1365-2249.1998.00557.x

  103. 103.
    Two Faces of Chondroitin Sulfate Proteoglycan in Spinal Cord Repair: A Role in Microglia/Macrophage Activation · 2008
    No notice
  104. 104.
    Selective Chemokine Receptor Usage by Central Nervous System Myeloid Cells in CCR2-Red Fluorescent Protein Knock-In Mice · 2010
    Corrected
  105. 105.

    Sargsyan S. A. Blackburn D. J. Barber S. C. Monk P. N. Shaw P. J. (2009 ). Mutant SOD1 G93A microglia have an inflammatory phenotype and elevated production of MCP-1. Neuroreport 20 1450–1455

    Not in our library10.1097/wnr.0b013e328331e8fa

  106. 106.

    Scheffel J. Regen T. Van Rossum D. Seifert S. Ribes S. Nau R. et al. (2012 ). Toll-like receptor activation reveals developmental reorganization and unmasks responder subsets of microglia. Glia 60 1930–1943

    Not in our library10.1002/glia.22409

  107. 107.

    Schulz C. Gomez Perdiguero E. Chorro L. Szabo-Rogers H. Cagnard N. Kierdorf K. et al. (2012 ). A lineage of myeloid cells independent of Myb and hematopoietic stem cells. Science 336 86–90

    Not in our library10.1126/science.1219179

  108. 108.

    Schwartz M. Butovsky O. Bruck W. Hanisch U. K. (2006 ). Microglial phenotype: is the commitment reversible? Trends Neurosci. 29 68–74

    Not in our library10.1016/j.tins.2005.12.005

  109. 109.

    Shaked I. Porat Z. Gersner R. Kipnis J. Schwartz M. (2004 ). Early activation of microglia as antigen-presenting cells correlates with T cell-mediated protection and repair of the injured central nervous system. J. Neuroimmunol. 146 84–93

    Not in our library10.1016/j.jneuroim.2003.10.049

  110. 110.

    Shaked I. Tchoresh D. Gersner R. Meiri G. Mordechai S. Xiao X. et al. (2005 ). Protective autoimmunity: interferon-gamma enables microglia to remove glutamate without evoking inflammatory mediators. J. Neurochem. 92 997–1009

    Not in our library10.1111/j.1471-4159.2004.02954.x

  111. 111.
    Infiltrating Blood-Derived Macrophages Are Vital Cells Playing an Anti-inflammatory Role in Recovery from Spinal Cord Injury in Mice · 2009
    No notice
  112. 112.

    Shechter R. Miller O. Yovel G. Rosenzweig N. London A. Ruckh J. et al. (2013 ). Recruitment of beneficial M2 macrophages to injured spinal cord is orchestrated by remote brain choroid plexus. Immunity

    Not in our library

  113. 113.
    The glial scar-monocyte interplay: a pivotal resolution phase in spinal cord repair. · 2011
    Not checked
  114. 114.

    Sica A. Mantovani A. (2012 ). Macrophage plasticity and polarization: in vivo veritas. J. Clin. Invest. 122 787–795

    Not in our library10.1172/jci59643

  115. 115.

    Sierra A. Encinas J. M. Deudero J. J. Chancey J. H. Enikolopov G. Overstreet-Wadiche L. S. et al. (2010 ). Microglia shape adult hippocampal neurogenesis through apoptosis-coupled phagocytosis. Cell Stem Cell 7 483–495

    Not in our library10.1016/j.stem.2010.08.014

  116. 116.

    Simard A. R. Soulet D. Gowing G. Julien J. P. Rivest S. (2006 ). Bone marrow-derived microglia play a critical role in restricting senile plaque formation in Alzheimer’s disease. Neuron 49 489–502

    Not in our library10.1016/j.neuron.2006.01.022

  117. 117.

    Smith P. D. Ochsenbauer-Jambor C. Smythies L. E. (2005 ). Intestinal macrophages: unique effector cells of the innate immune system. Immunol. Rev. 206 149–159

    Not in our library10.1111/j.0105-2896.2005.00288.x

  118. 118.

    Smith P. D. Smythies L. E. Shen R. Greenwell-Wild T. Gliozzi M. Wahl S. M. (2011 ). Intestinal macrophages and response to microbial encroachment. Mucosal Immunol. 4 31–42

    Not in our library10.1038/mi.2010.66

  119. 119.

    Stadelmann C. Kerschensteiner M. Misgeld T. Bruck W. Hohlfeld R. Lassmann H. (2002 ). BDNF and gp145trkB in multiple sclerosis brain lesions: neuroprotective interactions between immune and neuronal cells? Brain 125 75–85

    Not in our library10.1093/brain/awf015

  120. 120.

    Stalder M. Deller T. Staufenbiel M. Jucker M. (2001 ). 3D-Reconstruction of microglia and amyloid in APP23 transgenic mice: no evidence of intracellular amyloid. Neurobiol. Aging 22 427–434

    Not in our library10.1016/s0197-4580(01)00209-3

  121. 121.

    Stirling D. P. Khodarahmi K. Liu J. Mcphail L. T. Mcbride C. B. Steeves J. D. et al. (2004 ). Minocycline treatment reduces delayed oligodendrocyte death, attenuates axonal dieback, and improves functional outcome after spinal cord injury. J. Neurosci. 24 2182–2190

    Not in our library10.1523/jneurosci.5275-03.2004

  122. 122.

    Streit W. J. (2002 ). Microglia as neuroprotective, immunocompetent cells of the CNS. Glia 40 133–139

    Not in our library10.1002/glia.10154

  123. 123.

    Thored P. Heldmann U. Gomes-Leal W. Gisler R. Darsalia V. Taneera J. et al. (2009 ). Long-term accumulation of microglia with proneurogenic phenotype concomitant with persistent neurogenesis in adult subventricular zone after stroke. Glia 57 835–849

    Not in our library10.1002/glia.20810

  124. 124.

    Tremblay M. E. (2011 ). The role of microglia at synapses in the healthy CNS: novel insights from recent imaging studies. Neuron Glia Biol. 7 67–76

    Not in our library10.1017/s1740925x12000038

  125. 125.

    Turville S. G. Cameron P. U. Handley A. Lin G. Pohlmann S. Doms R. W. et al. (2002 ). Diversity of receptors binding HIV on dendritic cell subsets. Nat. Immunol. 3 975–983

    Not in our library10.1038/ni841

  126. 126.

    Uematsu S. Jang M. H. Chevrier N. Guo Z. Kumagai Y. Yamamoto M. et al. (2006 ). Detection of pathogenic intestinal bacteria by Toll-like receptor 5 on intestinal CD11c+ lamina propria cells. Nat. Immunol. 7 868–874

    Not in our library10.1038/ni1362

  127. 127.

    Varol C. Zigmond E. Jung S. (2010 ). Securing the immune tightrope: mononuclear phagocytes in the intestinal lamina propria. Nat. Rev. Immunol. 10 415–426

    Not in our library10.1038/nri2778

  128. 128.

    Vukovic J. Colditz M. J. Blackmore D. G. Ruitenberg M. J. Bartlett P. F. (2012 ). Microglia modulate hippocampal neural precursor activity in response to exercise and aging. J. Neurosci. 32 6435–6443

    Not in our library10.1523/jneurosci.5925-11.2012

  129. 129.

    Wake H. Moorhouse A. J. Jinno S. Kohsaka S. Nabekura J. (2009 ). Resting microglia directly monitor the functional state of synapses in vivo and determine the fate of ischemic terminals. J. Neurosci. 29 3974–3980

    Not in our library10.1523/jneurosci.4363-08.2009

  130. 130.

    Walton N. M. Sutter B. M. Laywell E. D. Levkoff L. H. Kearns S. M. Marshall G. P. II, et al. (2006 ). Microglia instruct subventricular zone neurogenesis. Glia 54 815–825

    Not in our library10.1002/glia.20419

  131. 131.

    Wang Y. Zhang T. Y. Xin J. Li T. Yu H. Li N. et al. (2012 ). Differential involvement of brain-derived neurotrophic factor in reconsolidation and consolidation of conditioned taste aversion memory. PLoS ONE 7:e49942

    Not in our library10.1371/journal.pone.0049942

  132. 132.

    Wegiel J. Wang K. C. Imaki H. Rubenstein R. Wronska A. Osuchowski M. et al. (2001 ). The role of microglial cells and astrocytes in fibrillar plaque evolution in transgenic APP(SW) mice. Neurobiol. Aging 22 49–61

    Not in our library10.1016/s0197-4580(00)00181-0

  133. 133.

    Wilson E. H. Weninger W. Hunter C. A. (2010 ). Trafficking of immune cells in the central nervous system. J. Clin. Invest. 120 1368–1379

    Not in our library10.1172/jci41911

  134. 134.

    Wolf S. A. Steiner B. Akpinarli A. Kammertoens T. Nassenstein C. Braun A. et al. (2009 ). CD4-positive T lymphocytes provide a neuroimmunological link in the control of adult hippocampal neurogenesis. J. Immunol. 182 3979–3984

    Not in our library10.4049/jimmunol.0801218

  135. 135.

    Wright D. E. Wagers A. J. Gulati A. P. Johnson F. L. Weissman I. L. (2001 ). Physiological migration of hematopoietic stem and progenitor cells. Science 294 1933–1936

    Not in our library10.1126/science.1064081

  136. 136.

    Yin Y. Henzl M. T. Lorber B. Nakazawa T. Thomas T. T. Jiang F. et al. (2006 ). Oncomodulin is a macrophage-derived signal for axon regeneration in retinal ganglion cells. Nat. Neurosci. 9 843–852

    Not in our library10.1038/nn1701

  137. 137.

    Ziv Y. Ron N. Butovsky O. Landa G. Sudai E. Greenberg N. et al. (2006 ). Immune cells contribute to the maintenance of neurogenesis and spatial learning abilities in adulthood. Nat. Neurosci. 9 268–275

    Not in our library10.1038/nn1629

  138. 138.

    Ziv Y. Schwartz M. (2008 ). Orchestrating brain-cell renewal: the role of immune cells in adult neurogenesis in health and disease. Trends Mol. Med. 14 471–478

    Not in our library10.1016/j.molmed.2008.09.004

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