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Reciprocal regulation of IL‐23 and IL‐12 following co‐activation of Dectin‐1 and TLR signaling pathways

Kevin M. Dennehy, Janet A. Willment, David L. Williams and 1 more

European Journal of Immunology · 2009

doi:10.1002/eji.200838543

Abstract

Recognition of microbial products by germ‐line‐encoded PRR initiates immune responses, but how PRR mediate specific host responses to infectious agents is poorly understood. We and others have proposed that specificity is achieved by collaborative responses mediated between different PRR. One such example comprises the fungal β‐glucan receptor Dectin‐1, which collaborates with TLR to induce TNF production. We show here that collaborative responses mediated by Dectin‐1 and TLR2 are more extensive than first appreciated, and result in enhanced IL‐23, IL‐6 and IL‐10 production in DC, while down‐regulating IL‐12 relative to the levels produced by TLR ligation alone. Such down‐regulation occurred with multiple MyD88‐coupled TLR, was dependent on signaling through Dectin‐1 and also occurred in macrophages. These findings explain how fungi can induce IL‐23 and IL‐6, while suppressing IL‐12, a combination which has previously been shown to contribute to the development of Th17 responses found during fungal infections. Furthermore, these data reveal how the collaboration of different PRR can tailor specific responses to infectious agents.

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References 34

  1. 1.

    O'Neill LA, Bowie AG. The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling. Nat. Rev. Immunol. 2007;7:353-364.

    Not in our library10.1038/nri2079

  2. 2.

    Dennehy KM, Brown GD. The role of the beta-glucan receptor Dectin-1 in control of fungal infection. J. Leukoc. Biol. 2007;82:253-258.

    Not in our library10.1189/jlb.1206753

  3. 3.

    Trinchieri G, Sher A. Cooperation of Toll-like receptor signals in innate immune defence. Nat. Rev. Immunol. 2007;7:179-190.

    Not in our library10.1038/nri2038

  4. 4.

    Napolitani G, Rinaldi A, Bertoni F, Sallusto F, Lanzavecchia A. Selected Toll-like receptor agonist combinations synergistically trigger a T helper type 1-polarizing program in dendritic cells. Nat. Immunol. 2005;6:769-776.

    Not in our library10.1038/ni1223

  5. 5.
  6. 6.

    Taylor PR, Tsoni SV, Willment JA, Dennehy KM, Rosas M, Findon H, Haynes K, et al. Dectin-1 is required for beta-glucan recognition and control of fungal infection. Nat. Immunol. 2007;8:31-38.

    Not in our library10.1038/ni1408

  7. 7.

    Brown GD. Dectin-1: a signalling non-TLR pattern-recognition receptor. Nat. Rev. Immunol. 2006;6:33-43.

    Not in our library10.1038/nri1745

  8. 8.

    Leibundgut-Landmann S, Gross O, Robinson MJ, Osorio F, Slack EC, Tsoni SV, Schweighoffer E, et al. Syk- and CARD9-dependent coupling of innate immunity to the induction of T helper cells that produce interleukin 17. Nat. Immunol. 2007;8:630-638.

    Not in our library10.1038/ni1460

  9. 9.

    Acosta-Rodriguez EV, Rivino L, Geginat J, Jarrossay D, Gattorno M, Lanzavecchia A, Sallusto F, Napolitani G. Surface phenotype and antigenic specificity of human interleukin 17-producing T helper memory cells. Nat. Immunol. 2007;8:639-646.

    Not in our library10.1038/ni1467

  10. 10.

    Rogers NC, Slack EC, Edwards AD, Nolte MA, Schulz O, Schweighoffer E, Williams DL, et al. Syk-dependent cytokine induction by dectin-1 reveals a novel pattern recognition pathway for C-type lectins. Immunity. 2005;22:507-517.

    Not in our library10.1016/j.immuni.2005.03.004

  11. 11.

    Williams DL, McNamee RB, Jones EL, Pretus HA, Ensley HE, Browder IW, Di Luzio NR. A method for the solubilization of a (1–>3)-beta-D-glucan isolated from Saccharomyces cerevisiae. Carbohydr. Res. 1991;219:203-213.

    Not in our library10.1016/0008-6215(91)89052-h

  12. 12.

    Dillon S, Agrawal A, Van Dyke T, Landreth G, McCauley L, Koh A, Maliszewski C, et al. A Toll-like receptor 2 ligand stimulates Th2 responses in vivo, via induction of extracellular signal-regulated kinase mitogen-activated protein kinase and c-Fos in dendritic cells. J. Immunol. 2004;172:4733-4743.

    Not in our library10.4049/jimmunol.172.8.4733

  13. 13.

    Gantner BN, Simmons RM, Canavera SJ, Akira S, Underhill DM. Collaborative Induction of Inflammatory Responses by Dectin-1 and Toll-like Receptor 2. J. Exp. Med. 2003;197:1107-1117.

    Not in our library10.1084/jem.20021787

  14. 14.

    Taylor PR, Brown GD, Reid DM, Willment JA, Martinez-Pomares L, Gordon S, Wong SYC. The beta-glucan receptor, Dectin-1, is predominantly expressed on the surface of cells of the monocyte/macrophage and neutrophil lineages. J. Immunol. 2002;269:3876-3882.

    Not in our library10.4049/jimmunol.169.7.3876

  15. 15.

    Dillon S, Agrawal S, Banerjee K, Letterio J, Denning TL, Oswald-Richter K, Kasprowicz DJ, et al. Yeast zymosan, a stimulus for TLR2 and dectin-1, induces regulatory antigen-presenting cells and immunological tolerance. J. Clin. Invest. 2006;116:916-928.

    Not in our library10.1172/jci27203

  16. 16.

    Slack EC, Robinson MJ, Hernanz-Falcon P, Brown GD, Williams DL, Schweighoffer E, Tybulewicz VL, Reis e Sousa C. Syk-dependent ERK activation regulates IL-2 and IL-10 production by DC stimulated with zymosan. Eur. J. Immunol. 2007;37:1600-1612.

    Not in our library10.1002/eji.200636830

  17. 17.

    Arbibe L, Mira JP, Teusch N, Kline L, Guha M, Mackman N, Godowski PJ, et al. Toll-like receptor 2-mediated NF-kappa B activation requires a Rac1-dependent pathway. Nat. Immunol. 2000;1:533-540.

    Not in our library10.1038/82797

  18. 18.

    Herre J, Marshall AJ, Caron E, Edwards AD, Williams DL, Schweighoffer E, Tybulewicz VL, et al. Dectin-1 utilizes novel mechanisms for yeast phagocytosis in macrophages. Blood. 2004;104:4038-4045.

    Not in our library10.1182/blood-2004-03-1140

  19. 19.

    Polumuri SK, Toshchakov VY, Vogel SN. Role of phosphatidylinositol-3 kinase in transcriptional regulation of TLR-induced IL-12 and IL-10 by Fc gamma receptor ligation in murine macrophages. J. Immunol. 2007;179:236-246.

    Not in our library10.4049/jimmunol.179.1.236

  20. 20.

    Fukao T, Tanabe M, Terauchi Y, Ota T, Matsuda S, Asano T, Kadowaki T, et al. PI3K-mediated negative feedback regulation of IL-12 production in DCs. Nat. Immunol. 2002;3:875-881.

    Not in our library10.1038/ni825

  21. 21.

    D'Andrea A, Aste-Amezaga M, Valiante NM, Ma X, Kubin M, Trinchieri G. Interleukin 10 (IL-10) inhibits human lymphocyte interferon gamma-production by suppressing natural killer cell stimulatory factor/IL-12 synthesis in accessory cells. J. Exp. Med. 1993;178:1041-1048.

    Not in our library10.1084/jem.178.3.1041

  22. 22.

    Netea MG, Brown GD, Kullberg BJ, Gow NA. An integrated model of the recognition of Candida albicans by the innate immune system. Nat. Rev. Microbiol. 2008;6:67-78.

    Not in our library10.1038/nrmicro1815

  23. 23.

    Rosas M, Liddiard K, Kimberg M, Faro-Trindade I, McDonald JU, Williams DL, Brown GD, Taylor PR. The induction of inflammation by dectin-1 in vivo is dependent on myeloid cell programming and the progression of phagocytosis. J. Immunol. 2008;181:3549-3557.

    Not in our library10.4049/jimmunol.181.5.3549

  24. 24.

    Goodridge HS, Shimada T, Wolf AJ, Hsu YM, Becker CA, Lin X, Underhill DM. Differential use of CARD9 by Dectin-1 in macrophages and dendritic cells. J. Immunol. 2009;182:1146-1154.

    Not in our library10.4049/jimmunol.182.2.1146

  25. 25.

    Gerosa F, Baldani-Guerra B, Lyakh LA, Batoni G, Esin S, Winkler-Pickett RT, Consolaro MR, et al. Differential regulation of interleukin 12 and interleukin 23 production in human dendritic cells. J. Exp. Med. 2008;205:1447-1461.

    Not in our library10.1084/jem.20071450

  26. 26.

    Gerber JS, Mosser DM. Reversing lipopolysaccharide toxicity by ligating the macrophage Fc gamma receptors. J. Immunol. 2001;166:6861-6868.

    Not in our library10.4049/jimmunol.166.11.6861

  27. 27.

    Watanabe T, Kitani A, Murray PJ, Strober W. NOD2 is a negative regulator of Toll-like receptor 2-mediated T helper type 1 responses. Nat. Immunol. 2004;5:800-808.

    Not in our library10.1038/ni1092

  28. 28.

    van Beelen AJ, Zelinkova Z, Taanman-Kueter EW, Muller FJ, Hommes DW, Zaat SA, Kapsenberg ML, de Jong EC. Stimulation of the intracellular bacterial sensor NOD2 programs dendritic cells to promote interleukin-17 production in human memory T cells. Immunity. 2007;27:660-669.

    Not in our library10.1016/j.immuni.2007.08.013

  29. 29.

    Gross O, Gewies A, Finger K, Schafer M, Sparwasser T, Peschel C, Forster I, Ruland J. Card9 controls a non-TLR signalling pathway for innate anti-fungal immunity. Nature. 2006;442:651-656.

    Not in our library10.1038/nature04926

  30. 30.

    Hsu YM, Zhang Y, You Y, Wang D, Li H, Duramad O, Qin XF, et al. The adaptor protein CARD9 is required for innate immune responses to intracellular pathogens. Nat. Immunol. 2007;8:198-205.

    Not in our library10.1038/ni1426

  31. 31.

    Hara H, Ishihara C, Takeuchi A, Imanishi T, Xue L, Morris SW, Inui M, et al. The adaptor protein CARD9 is essential for the activation of myeloid cells through ITAM-associated and Toll-like receptors. Nat. Immunol. 2007;8:619-629.

    Not in our library10.1038/ni1466

  32. 32.

    Brown GD, Herre J, Williams DL, Willment JA, Marshall ASJ, Gordon S. Dectin-1 mediates the biological effects of beta-glucan. J. Exp. Med. 2003;197:1119-1124.

    Not in our library10.1084/jem.20021890

  33. 33.

    Lutz MB, Kukutsch N, Ogilvie AL, Rossner S, Koch F, Romani N, Schuler G. An advanced culture method for generating large quantities of highly pure dendritic cells from mouse bone marrow. J. Immunol. Methods. 1999;223:77-92.

    Not in our library10.1016/s0022-1759(98)00204-x

  34. 34.

    Liu Z, Jiu J, Liu S, Fa X, Li F, Du Y. Blockage of tumor necrosis factor prevents intestinal mucosal inflammation through down-regulation of interleukin-23 secretion. J. Autoimmun. 2007;29:187-194.

    Not in our library10.1016/j.jaut.2007.07.004

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