Enhanced protection to Mycobacterium tuberculosis infection in IL‐10‐deficient mice is accompanied by early and enhanced Th1 responses in the lung

Abstract

IL‐10 regulates the balance of an immune response between pathogen clearance and immunopathology. We show here that Mycobacterium tuberculosis ( Mtb ) infection in the absence of IL‐10 (IL‐10 −/− mice) results in reduced bacterial loads in the lung. This reduction was preceded by an accelerated and enhanced IFN‐γ response in the lung, an increased influx of CD4 + T cells into the lung, and enhanced production of chemokines and cytokines, including CXCL10 and IL‐17, in both the lung and the serum. Neutralization of IL‐17 affected neither the enhanced production of CXCL10 nor the accumulation of IFN‐γ‐producing T cells in the lungs, but led to reduced numbers of granulocytes in the lung and reduced bacterial loads in the spleens of Mtb ‐infected mice. This suggests that IL‐17 may contribute to dissemination of Mtb .

Shown for reading. Its publisher allows quoting it, not republishing it.

References 56

1. 1.

   Cooper AM. Cell-mediated immune responses in tuberculosis. Annu. Rev. Immunol. 2009;27:393-422.

   Not in our library10.1146/annurev.immunol.021908.132703

2. 2.

   Flynn JL, Chan J. Immunology of tuberculosis. Annu. Rev. Immunol. 2001;19:93-129.

   Not in our library10.1146/annurev.immunol.19.1.93

3. 3.

   North RJ, Jung YJ. Immunity to tuberculosis. Annu. Rev. Immunol. 2004;22:599-623.

   Not in our library10.1146/annurev.immunol.22.012703.104635

4. 4.

   Cooper AM, Dalton DK, Stewart TA, Griffin JP, Russell DG, Orme IM. Disseminated tuberculosis in interferon gamma gene-disrupted mice. J. Exp. Med. 1993;178:2243-2247.

   Not in our library10.1084/jem.178.6.2243

5. 5.

   Flynn JL, Chan J, Triebold KJ, Dalton DK, Stewart TA, Bloom BR. An essential role for interferon gamma in resistance to Mycobacterium tuberculosis infection. J. Exp. Med. 1993;178:2249-2254.

   Not in our library10.1084/jem.178.6.2249

6. 6.

   Casanova JL, Abel L. Genetic dissection of immunity to mycobacteria: the human model. Annu. Rev. Immunol. 2002;20:581-620.

   Not in our library10.1146/annurev.immunol.20.081501.125851

7. 7.

   Chackerian AA, Perera TV, Behar SM. Gamma interferon-producing CD4+T lymphocytes in the lung correlate with resistance to infection with Mycobacterium tuberculosis. Infect. Immun. 2001;69:2666-2674.

   Not in our library10.1128/iai.69.4.2666-2674.2001

8. 8.

   Khader SA, Bell GK, Pearl JE, Fountain JJ, Rangel-Moreno J, Cilley GE, et al. IL-23 and IL-17 in the establishment of protective pulmonary CD4+T cell responses after vaccination and during Mycobacterium tuberculosis challenge. Nat. Immunol. 2007;8:369-377.

   Not in our library10.1038/ni1449

9. 9.

   Lockhart E, Green AM, Flynn JL. IL-17 production is dominated by gammadelta T cells rather than CD4 T cells during Mycobacterium tuberculosis infection. J. Immunol. 2006;177:4662-4669.

   Not in our library10.4049/jimmunol.177.7.4662

10. 10.

    Aujla SJ, Chan YR, Zheng M, Fei M, Askew DJ, Pociask DA, Reinhart TA, et al. IL-22 mediates mucosal host defense against Gram-negative bacterial pneumonia. Nat. Med. 2008;14:275-281.

    Not in our library10.1038/nm1710

11. 11.

    Aujla SJ, Dubin PJ, Kolls JK. Th17 cells and mucosal host defense. Semin. Immunol. 2007;19:377-382.

    Not in our library10.1016/j.smim.2007.10.009

12. 12.

    Flynn JL, Goldstein MM, Chan J, Triebold KJ, Pfeffer K, Lowenstein CJ, Schreiber R, et al. Tumor necrosis factor-alpha is required in the protective immune response against Mycobacterium tuberculosis in mice. Immunity. 1995;2:561-572.

    Not in our library10.1016/1074-7613(95)90001-2

13. 13.

    Keane J, Gershon S, Wise RP, Mirabile-Levens E, Kasznica J, Schwieterman WD, Siegel JN, Braun MM. Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. N. Engl. J. Med. 2001;345:1098-1104.

    Not in our library10.1056/nejmoa011110

14. 14.

    MacMicking JD, North RJ, LaCourse R, Mudgett JS, Shah SK, Nathan CF. Identification of nitric oxide synthase as a protective locus against tuberculosis. Proc. Natl. Acad. Sci. USA. 1997;94:5243-5248.

    Not in our library10.1073/pnas.94.10.5243

15. 15.

    Moore KW, de Waal Malefyt R, Coffman RL, O'Garra A. Interleukin-10 and the interleukin-10 receptor. Annu. Rev. Immunol. 2001;19:683-765.

    Not in our library10.1146/annurev.immunol.19.1.683

16. 16.

    O'Garra A, Barrat FJ, Castro AG, Vicari A, Hawrylowicz C. Strategies for use of IL-10 or its antagonists in human disease. Immunol. Rev. 2008;223:114-131.

    Not in our library10.1111/j.1600-065x.2008.00635.x

17. 17.

    Gazzinelli RT, Wysocka M, Hieny S, Scharton-Kersten T, Cheever A, Kuhn R, Muller W, et al. In the absence of endogenous IL-10, mice acutely infected with Toxoplasma gondii succumb to a lethal immune response dependent on CD4+T cells and accompanied by overproduction of IL-12, IFN-gamma and TNF-alpha. J. Immunol. 1996;157:798-805.

    Not in our library

18. 18.

    Li C, Corraliza I, Langhorne J. A defect in interleukin-10 leads to enhanced malarial disease in Plasmodium chabaudi infection in mice. Infect. Immun. 1999;67:4435-4442.

    Not in our library10.1128/iai.67.9.4435-4442.1999

19. 19.

    Belkaid Y, Hoffmann KF, Mendez S, Kamhawi S, Udey MC, Wynn TA, Sacks DL. The role of interleukin (IL)-10 in the persistence of Leishmania major in the skin after healing and the therapeutic potential of anti-IL-10 receptor antibody for sterile cure. J. Exp. Med. 2001;194:1497-1506.

    Not in our library10.1084/jem.194.10.1497

20. 20.

    Brooks DG, Trifilo MJ, Edelmann KH, Teyton L, McGavern DB, Oldstone MB. Interleukin-10 determines viral clearance or persistence in vivo. Nat. Med. 2006;12:1301-1309.

    Not in our library10.1038/nm1492

21. 21.

    Ejrnaes M, Filippi CM, Martinic MM, Ling EM, Togher LM, Crotty S, von Herrath MG. Resolution of a chronic viral infection after interleukin-10 receptor blockade. J. Exp. Med. 2006;203:2461-2472.

    Not in our library10.1084/jem.20061462

22. 22.

    Silva RA, Appelberg R. Blocking the receptor for interleukin 10 protects mice from lethal listeriosis. Antimicrob. Agents Chemother. 2001;45:1312-1314.

    Not in our library10.1128/aac.45.4.1312-1314.2001

23. 23.

    Jung YJ, Ryan L, LaCourse R, North RJ. Increased interleukin-10 expression is not responsible for failure of T helper 1 immunity to resolve airborne Mycobacterium tuberculosis infection in mice. Immunology. 2003;109:295-299.

    Not in our library10.1046/j.1365-2567.2003.01645.x

24. 24.

    Boussiotis VA, Tsai EY, Yunis EJ, Thim S, Delgado JC, Dascher CC, Berezovskaya A, et al. IL-10-producing T cells suppress immune responses in anergic tuberculosis patients. J. Clin. Invest. 2000;105:1317-1325.

    Not in our library10.1172/jci9918

25. 25.

    Gerosa F, Nisii C, Righetti S, Micciolo R, Marchesini M, Cazzadori A, Trinchieri G. CD4(+) T cell clones producing both interferon-gamma and interleukin-10 predominate in bronchoalveolar lavages of active pulmonary tuberculosis patients. Clin. Immunol. 1999;92:224-234.

    Not in our library10.1006/clim.1999.4752

26. 26.

    Gong JH, Zhang M, Modlin RL, Linsley PS, Iyer D, Lin Y, Barnes PF. Interleukin-10 downregulates Mycobacterium tuberculosis-induced Th1 responses and CTLA-4 expression. Infect. Immun. 1996;64:913-918.

    Not in our library10.1128/iai.64.3.913-918.1996

27. 27.

    Verbon A, Juffermans N, Van Deventer SJ, Speelman P, Van Deutekom H, Van Der Poll T. Serum concentrations of cytokines in patients with active tuberculosis (TB) and after treatment. Clin. Exp. Immunol. 1999;115:110-113.

    Not in our library10.1046/j.1365-2249.1999.00783.x

28. 28.

    Roach DR, Martin E, Bean AG, Rennick DM, Briscoe H, Britton WJ. Endogenous inhibition of antimycobacterial immunity by IL-10 varies between mycobacterial species. Scand. J. Immunol. 2001;54:163-170.

    Not in our library10.1046/j.1365-3083.2001.00952.x

29. 29.

    Roque S, Nobrega C, Appelberg R, Correia-Neves M. IL-10 underlies distinct susceptibility of BALB/c and C57BL/6 mice to Mycobacterium avium infection and influences efficacy of antibiotic therapy. J. Immunol. 2007;178:8028-8035.

    Not in our library10.4049/jimmunol.178.12.8028

30. 30.

    Jacobs M, Brown N, Allie N, Gulert R, Ryffel B. Increased resistance to mycobacterial infection in the absence of interleukin-10. Immunology. 2000;100:494-501.

    Not in our library10.1046/j.1365-2567.2000.00053.x

31. 31.

    Murray PJ, Young RA. Increased antimycobacterial immunity in interleukin-10-deficient mice. Infect. Immun. 1999;67:3087-3095.

    Not in our library10.1128/iai.67.6.3087-3095.1999

32. 32.

    Higgins DM, Sanchez-Campillo J, Rosas-Taraco AG, Lee EJ, Orme IM, Gonzalez-Juarrero M. Lack of IL-10 alters inflammatory and immune responses during pulmonary Mycobacterium tuberculosis infection. Tuberculosis (Edinb). 2009;89:149-157.

    Not in our library10.1016/j.tube.2009.01.001

33. 33.

    North RJ. Mice incapable of making IL-4 or IL-10 display normal resistance to infection with Mycobacterium tuberculosis. Clin. Exp. Immunol. 1998;113:55-58.

    Not in our library10.1046/j.1365-2249.1998.00636.x

34. 34.

    Beamer GL, Flaherty DK, Assogba BD, Stromberg P, Gonzalez-Juarrero M, de Waal Malefyt R, Vesosky B, Turner J. Interleukin-10 promotes Mycobacterium tuberculosis disease progression in CBA/J mice. J. Immunol. 2008;181:5545-5550.

    Not in our library10.4049/jimmunol.181.8.5545

35. 35.

    Turner J, Gonzalez-Juarrero M, Ellis DL, Basaraba RJ, Kipnis A, Orme IM, Cooper AM. In vivo IL-10 production reactivates chronic pulmonary tuberculosis in C57BL/6 mice. J. Immunol. 2002;169:6343-6351.

    Not in our library10.4049/jimmunol.169.11.6343

36. 36.

    Skold M, Behar SM. Tuberculosis triggers a tissue-dependent program of differentiation and acquisition of effector functions by circulating monocytes. J. Immunol. 2008;181:6349-6360.

    Not in our library10.4049/jimmunol.181.9.6349

37. 37.

    Wolf AJ, Linas B, Trevejo-Nunez GJ, Kincaid E, Tamura T, Takatsu K, Ernst JD. Mycobacterium tuberculosis infects dendritic cells with high frequency and impairs their function in vivo. J. Immunol. 2007;179:2509-2519.

    Not in our library10.4049/jimmunol.179.4.2509

38. 38.

    Bhatt K, Hickman SP, Salgame P. Cutting edge: a new approach to modeling early lung immunity in murine tuberculosis. J. Immunol. 2004;172:2748-2751.

    Not in our library10.4049/jimmunol.172.5.2748

39. 39.

    Demangel C, Bertolino P, Britton WJ. Autocrine IL-10 impairs dendritic cell (DC)-derived immune responses to mycobacterial infection by suppressing DC trafficking to draining lymph nodes and local IL-12 production. Eur. J. Immunol. 2002;32:994-1002.

    Not in our library10.1002/1521-4141(200204)32:4<994::aid-immu994>3.0.co;2-6

40. 40.

    Humphreys IR, Stewart GR, Turner DJ, Patel J, Karamanou D, Snelgrove RJ, Young DB. A role for dendritic cells in the dissemination of mycobacterial infection. Microbes Infect. 2006;8:1339-1346.

    Not in our library10.1016/j.micinf.2005.12.023

41. 41.

    Khader SA, Partida-Sanchez S, Bell G, Jelley-Gibbs DM, Swain S, Pearl JE, Ghilardi N, et al. Interleukin 12p40 is required for dendritic cell migration and T cell priming after Mycobacterium tuberculosis infection. J. Exp. Med. 2006;203:1805-1815.

    Not in our library10.1084/jem.20052545

42. 42.

    Chackerian AA, Alt JM, Perera TV, Dascher CC, Behar SM. Dissemination of Mycobacterium tuberculosis is influenced by host factors and precedes the initiation of T-cell immunity. Infect. Immun. 2002;70:4501-4509.

    Not in our library10.1128/iai.70.8.4501-4509.2002

43. 43.

    Reiley WW, Calayag MD, Wittmer ST, Huntington JL, Pearl JE, Fountain JJ, Martino CA, et al. ESAT-6-specific CD4 T cell responses to aerosol Mycobacterium tuberculosis infection are initiated in the mediastinal lymph nodes. Proc. Natl. Acad. Sci. USA. 2008;105:10961-10966.

    Not in our library10.1073/pnas.0801496105

44. 44.

    Wolf AJ, Desvignes L, Linas B, Banaiee N, Tamura T, Takatsu K, Ernst JD. Initiation of the adaptive immune response to Mycobacterium tuberculosis depends on antigen production in the local lymph node, not the lungs. J. Exp. Med. 2008;205:105-115.

    Not in our library10.1084/jem.20071367

45. 45.

    Ye P, Rodriguez FH, Kanaly S, Stocking KL, Schurr J, Schwarzenberger P, Oliver P, et al. Requirement of interleukin 17 receptor signaling for lung CXC chemokine and granulocyte colony-stimulating factor expression, neutrophil recruitment, and host defense. J. Exp. Med. 2001;194:519-527.

    Not in our library10.1084/jem.194.4.519

46. 46.

    Khan IA, MacLean JA, Lee FS, Casciotti L, DeHaan E, Schwartzman JD, Luster AD. IP-10 is critical for effector T cell trafficking and host survival in Toxoplasma gondii infection. Immunity. 2000;12:483-494.

    Not in our library10.1016/s1074-7613(00)80200-9

47. 47.

    Gonzalez-Juarrero M, Hattle JM, Izzo A, Junqueira-Kipnis AP, Shim TS, Trapnell BC, et al. Disruption of granulocyte macrophage-colony stimulating factor production in the lungs severely affects the ability of mice to control Mycobacterium tuberculosis infection. J. Leukoc. Biol. 2005;77:914-922.

    Not in our library10.1189/jlb.1204723

48. 48.

    Abadie V, Badell E, Douillard P, Ensergueix D, Leenen PJ, Tanguy M, Fiette L, et al. Neutrophils rapidly migrate via lymphatics after Mycobacterium bovis BCG intradermal vaccination and shuttle live bacilli to the draining lymph nodes. Blood. 2005;106:1843-1850.

    Not in our library10.1182/blood-2005-03-1281

49. 49.

    Eum SY, Kong JH, Hong MS, Lee YJ, Kim JH, Hwang SH, Cho SN, et al. Neutrophils are the predominant infected phagocytic cells in the airways of patients with active pulmonary tuberculosis. Chest. 2010;137:122-128.

    Not in our library10.1378/chest.09-0903

50. 50.

    Seiler P, Aichele P, Bandermann S, Hauser AE, Lu B, Gerard NP, Gerard C, et al. Early granuloma formation after aerosol Mycobacterium tuberculosis infection is regulated by neutrophils via CXCR3-signaling chemokines. Eur. J. Immunol. 2003;33:2676-2686.

    Not in our library10.1002/eji.200323956

51. 51.

    Eruslanov EB, Lyadova IV, Kondratieva TK, Majorov KB, Scheglov IV, Orlova MO, Apt AS. Neutrophil responses to Mycobacterium tuberculosis infection in genetically susceptible and resistant mice. Infect. Immun. 2005;73:1744-1753.

    Not in our library10.1128/iai.73.3.1744-1753.2005

52. 52.

    Keller C, Hoffmann R, Lang R, Brandau S, Hermann C, Ehlers S. Genetically determined susceptibility to tuberculosis in mice causally involves accelerated and enhanced recruitment of granulocytes. Infect. Immun. 2006;74:4295-4309.

    Not in our library10.1128/iai.00057-06

53. 53.

    Barnes PF, Leedom JM, Chan LS, Wong SF, Shah J, Vachon LA, Overturf GD, Modlin RL. Predictors of short-term prognosis in patients with pulmonary tuberculosis. J. Infect. Dis. 1988;158:366-371.

    Not in our library10.1093/infdis/158.2.366

54. 54.

    Bandara A, Bremner S, Barker RD, Packe G, Griffiths C, Martineau A. Neutrophilia in tuberculosis. Thorax. 2008;63:A114.

    Not in our library

55. 55.

    Zhang X, Majlessi L, Deriaud E, Leclerc C, Lo-Man R. Coactivation of Syk kinase and MyD88 adaptor protein pathways by bacteria promotes regulatory properties of neutrophils. Immunity. 2009;31:761-771.

    Not in our library10.1016/j.immuni.2009.09.016

56. 56.

    Shoemaker J, Saraiva M, O'Garra A. GATA-3 directly remodels the IL-10 locus independently of IL-4 in CD4+T cells. J. Immunol. 2006;176:3470-3479.

    Not in our library10.4049/jimmunol.176.6.3470

Cited by papers we hold 9

• Intracellular Pathogens: Host Immunity and Microbial Persistence Strategies · 2019
  No notice
• The Immunoregulation of Th17 in Host against Intracellular Bacterial Infection · 2018
  Not checked
• Immune Responses to Bacillus Calmette–Guérin Vaccination: Why Do They Fail to Protect against Mycobacterium tuberculosis? · 2017
  No notice
• Cellular and humoral immunogenicity of recombinant Mycobacterium smegmatis expressing Ag85B epitopes in mice · 2016
  Not checked
• Different human vaccine adjuvants promote distinct antigen-independent immunological signatures tailored to different pathogens · 2016
  No notice
• Type I IFN Induces IL-10 Production in an IL-27–Independent Manner and Blocks Responsiveness to IFN-γ for Production of IL-12 and Bacterial Killing in Mycobacterium tuberculosis –Infected Macrophages · 2014
  No notice
• The tuberculosis vaccine candidate Bacillus Calmette-Guérin ΔureC::hly coexpressing human interleukin-7 or -18 enhances antigen-specific T cell responses in mice. · 2013
  Not checked
• CD4-CD8-αβ and γδ T cells display inflammatory and regulatory potentials during human tuberculosis. · 2012
  Not checked
• Suboptimal Activation of Antigen-Specific CD4+ Effector Cells Enables Persistence of M. tuberculosis In Vivo · 2011
  No notice

Reads

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.