CR3 and Dectin-1 Collaborate in Macrophage Cytokine Response through Association on Lipid Rafts and Activation of Syk-JNK-AP-1 Pathway

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The incidence of life-threatening fungal infections is increasing during the last decades. A better understanding of the interactions between fungal pathogen and its host cell is important to the development of new therapeutic strategies against fungal infections. Dimorphic fungus Histoplasma capsulatum becomes disseminated and threatens life in immunocompromised individuals. This fungal pathogen utilizes complement receptor 3 (CR3) and Dectin-1, two pattern recognition receptors on the surface of innate immune cells, to induce macrophage cytokine response. In this study, we demonstrated that CR3 and Dectin-1 act collaboratively to induce macrophage TNF and IL-6 response through a mechanism dependent on activation of the Syk-JNK-AP-1 signaling axis. CR3 and Dectin-1 are recruited and form clusters on lipid raft microdomains upon stimulation by H. capsulatum, leading to activation of their signaling convergence at Syk kinase and induction of subsequent cytokine response. In addition, we showed that CR3 and Dectin-1 cooperatively instruct the adaptive antifungal immunity to defense against H. capsulatum infection. Our findings define the molecular mechanisms underlying receptor crosstalk between CR3 and Dectin-1 and provide a valuable model for receptor collaboration in the context of host-fungus interactions.

Vyšlo v časopise: CR3 and Dectin-1 Collaborate in Macrophage Cytokine Response through Association on Lipid Rafts and Activation of Syk-JNK-AP-1 Pathway. PLoS Pathog 11(7): e32767. doi:10.1371/journal.ppat.1004985
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004985

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1. Brown GD, Denning DW, Levitz SM. Tackling human fungal infections. Science. 2012;336(6082):647. doi: 10.1126/science.1222236 22582229.

2. Gordon S. Pattern recognition receptors: doubling up for the innate immune response. Cell. 2002;111(7):927–30. 12507420.

3. Brown GD. Innate antifungal immunity: the key role of phagocytes. Annu Rev Immunol. 2011;29:1–21. doi: 10.1146/annurev-immunol-030409-101229 20936972.

4. Guimaraes AJ, de Cerqueira MD, Nosanchuk JD. Surface architecture of Histoplasma capsulatum. Front Microbiol. 2011;2:225. doi: 10.3389/fmicb.2011.00225 22121356.

5. Smits GJ, Kapteyn JC, van den Ende H, Klis FM. Cell wall dynamics in yeast. Curr Opin Microbiol. 1999;2(4):348–52. 10458981.

6. Hontelez S, Sanecka A, Netea MG, van Spriel AB, Adema GJ. Molecular view on PRR cross-talk in antifungal immunity. Cell Microbiol 2012;14(4):467–74. doi: 10.1111/j.1462-5822.2012.01748.x 22233321.

7. 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(9):1107–17. doi: 10.1084/jem.20021787 12719479.

8. Brown GD, Herre J, Williams DL, Willment JA, Marshall AS, Gordon S. Dectin-1 mediates the biological effects of beta-glucans. J Exp Med. 2003;197(9):1119–24. doi: 10.1084/jem.20021890 12719478.

9. Dennehy KM, Ferwerda G, Faro-Trindade I, Pyz E, Willment JA, Taylor PR, et al. Syk kinase is required for collaborative cytokine production induced through Dectin-1 and Toll-like receptors. Eur J Immunol. 2008;38(2):500–6. doi: 10.1002/eji.200737741 18200499.

10. Ferwerda G, Meyer-Wentrup F, Kullberg B-J, Netea MG, Adema GJ. Dectin-1 synergizes with TLR2 and TLR4 for cytokine production in human primary monocytes and macrophages. Cell Microbiol. 2008;10(10):2058–66. doi: 10.1111/j.1462-5822.2008.01188.x 18549457.

11. Takahara K, Tokieda S, Nagaoka K, Takeda T, Kimura Y, Inaba K. C-type lectin SIGNR1 enhances cellular oxidative burst response against C. albicans in cooperation with Dectin-1. Eur J Immunol. 2011;41(5):1435–44. doi: 10.1002/eji.200940188 21400494.

12. Robinson MJ, Osorio F, Rosas M, Freitas RP, Schweighoffer E, Groß O, et al. Dectin-2 is a Syk-coupled pattern recognition receptor crucial for Th17 responses to fungal infection. J Exp Med. 2009;206(9):2037–51. doi: 10.1084/jem.20082818 19703985.

13. Lin JS, Huang JH, Hung LY, Wu SY, Wu-Hsieh BA. Distinct roles of complement receptor 3, Dectin-1, and sialic acids in murine macrophage interaction with Histoplasma yeast. J Leukoc Biol. 2010;88(1):95–106. doi: 10.1189/jlb.1109717 20360401.

14. Arnaout MA. Structure and function of the leukocyte adhesion molecules CD11/CD18. Blood. 1990;75(5):1037–50. 1968349.

15. Vetvicka V, Thornton BP, Ross GD. Soluble beta-glucan polysaccharide binding to the lectin site of neutrophil or natural killer cell complement receptor type 3 (CD11b/CD18) generates a primed state of the receptor capable of mediating cytotoxicity of iC3b-opsonized target cells. J Clin Invest. 1996;98(1):50–61. doi: 10.1172/JCI118777 8690804.

16. Mayadas TN, Cullere X. Neutrophil β2 integrins: moderators of life or death decisions. Trends Immunol. 2005;26(7):388–95. doi: 10.1016/j.it.2005.05.002 15922663.

17. Abram CL, Lowell CA. The Ins and Outs of Leukocyte Integrin Signaling. Annu Rev Immunol. 2009;27(1):339–62. doi: 10.1146/annurev.immunol.021908.132554 19302044.

18. Harokopakis E, Hajishengallis G. Integrin activation by bacterial fimbriae through a pathway involving CD14, Toll-like receptor 2, and phosphatidylinositol-3-kinase. Eur J Immunol. 2005;35(4):1201–10. doi: 10.1002/eji.200425883 15739163.

19. Li X, Utomo A, Cullere X, Choi Myunghwan M, Milner Danny A Jr, Venkatesh D, et al. The β-Glucan receptor Dectin-1 activates the integrin Mac-1 in neutrophils via Vav protein signaling to promote Candida albicans clearance. Cell Host Microbe. 2011;10(6):603–15. doi: 10.1016/j.chom.2011.10.009 22177564.

20. Groves E, Dart AE, Covarelli V, Caron E. Molecular mechanisms of phagocytic uptake in mammalian cells. Cell Mol Life Sci. 2008;65(13):1957–76. doi: 10.1007/s00018-008-7578-4 18322649.

21. Brown GD. Dectin-1: a signalling non-TLR pattern-recognition receptor. Nat Rev Immunol. 2006;6(1):33–43. doi: 10.1038/nri1745 16341139.

22. Xu S, Huo J, Lee K- G, Kurosaki T, Lam K- P. Phospholipase Cγ2 is critical for Dectin-1-mediated Ca2+ flux and cytokine production in dendritic cells. J Biol Chem. 2009;284(11):7038–46. doi: 10.1074/jbc.M806650200 19136564.

23. Goodridge HS, Simmons RM, Underhill DM. Dectin-1 stimulation by Candida albicans yeast or zymosan triggers NFAT activation in macrophages and dendritic cells. J Immunol. 2007;178(5):3107–15. 17312158.

24. Gross O, Gewies A, Finger K, Schäfer M, Sparwasser T, Peschel C, et al. Card9 controls a non-TLR signalling pathway for innate anti-fungal immunity. Nature. 2006;442(7103):651–6. doi: 10.1038/nature04926 16862125.

25. Jia XM, Tang B, Zhu LL, Liu YH, Zhao XQ, Gorjestani S, et al. CARD9 mediates Dectin-1-induced ERK activation by linking Ras-GRF1 to H-Ras for antifungal immunity. J Exp Med. 2014;211(11):2307–21. doi: 10.1084/jem.20132349 25267792.

26. Gringhuis SI, den Dunnen J, Litjens M, van der Vlist M, Wevers B, Bruijns SCM, et al. Dectin-1 directs T helper cell differentiation by controlling noncanonical NF-kappaB activation through Raf-1 and Syk. Nat Immunol. 2009;10(2):203–13. doi: 10.1038/ni.1692 19122653.

27. Goodridge HS, Shimada T, Wolf AJ, Hsu Y-MS, Becker CA, Lin X, et al. Differential use of CARD9 by Dectin-1 in macrophages and dendritic cells. J Immunol. 2009;182(2):1146–54. doi: 10.4049/jimmunol.182.2.1146 19124758.

28. Underhill DM, Rossnagle E, Lowell CA, Simmons RM. Dectin-1 activates Syk tyrosine kinase in a dynamic subset of macrophages for reactive oxygen production. Blood. 2005;106(7):2543–50. doi: 10.1182/blood-2005-03-1239 15956283.

29. Li B, Allendorf DJ, Hansen R, Marroquin J, Ding C, Cramer DE, et al. Yeast β-glucan amplifies phagocyte killing of iC3b-opsonized tumor cells via complement receptor 3-Syk-phosphatidylinositol 3-kinase pathway. J Immunol. 2006;177(3):1661–9. 16849475.

30. Pande G. The role of membrane lipids in regulation of integrin functions. Curr Opin Cell Biol 2000;12(5):569–74. 10978891.

31. Xu S, Huo J, Gunawan M, Su I-H, Lam K-P. Activated Dectin-1 localizes to lipid raft microdomains for signaling and activation of phagocytosis and cytokine production in dendritic cells. J Biol Chem. 2009;284(33):22005–11. doi: 10.1074/jbc.M109.009076 19525229.

32. Wu-Hsieh BA, Lee GS, Franco M, Hofman FM. Early activation of splenic macrophages by tumor necrosis factor alpha is important in determining the outcome of experimental histoplasmosis in mice. Infect Immun. 1992;60(10):4230–8. 1398934.

33. Rappleye CA, Eissenberg LG, Goldman WE. Histoplasma capsulatum α-(1,3)-glucan blocks innate immune recognition by the β-glucan receptor. Proc Natl Acad Sci U S A. 2007;104(4):1366–70. doi: 10.1073/pnas.0609848104 17227865.

34. Gantner BN, Simmons RM, Underhill DM. Dectin-1 mediates macrophage recognition of Candida albicans yeast but not filaments. EMBO J. 2005;24(6):1277–86. doi: 10.1038/sj.emboj.7600594 15729357.

35. Saijo S, Iwakura Y. Dectin-1 and Dectin-2 in innate immunity against fungi. Int Immunol. 2011;23(8):467–72. doi: 10.1093/intimm/dxr046 21677049.

36. Ratnoff WD, Pepple JM, Winkelstein JA. Activation of the alternative complement pathway by Histoplasma capsulatum. Infect Immun. 1980;30(1):147–9. 7439970.

37. Goodridge HS, Reyes CN, Becker CA, Katsumoto TR, Ma J, Wolf AJ, et al. Activation of the innate immune receptor Dectin-1 upon formation of a 'phagocytic synapse'. Nature. 2011;472(7344):471–5. doi: 10.1038/nature10071 21525931.

38. Inoue M, Moriwaki Y, Arikawa T, Chen YH, Oh YJ, Oliver T, et al. Cutting edge: critical role of intracellular osteopontin in antifungal innate immune responses. J Immunol. 2011;186(1):19–23. doi: 10.4049/jimmunol.1002735 21135164.

39. Wu-Hsieh BA, Howard DH. Inhibition of the intracellular growth of Histoplasma capsulatum by recombinant murine gamma interferon. Infect Immun. 1987;55(4):1014–6. 3104206.

40. Lin JS, Yang CW, Wang DW, Wu-Hsieh BA. Dendritic cells cross-present exogenous fungal antigens to stimulate a protective CD8 T cell response in infection by Histoplasma capsulatum. J Immunol. 2005;174(10):6282–91. 15879127.

41. Wu SY, Yu JS, Liu FT, Miaw SC, Wu-Hsieh BA. Galectin-3 negatively regulates dendritic cell production of IL-23/IL-17-axis cytokines in infection by Histoplasma capsulatum. J Immunol. 2013;190(7):3427–37. doi: 10.4049/jimmunol.1202122 23455499.

42. Subramanian Vignesh K, Landero Figueroa JA, Porollo A, Caruso JA, Deepe GS Jr. Granulocyte macrophage-colony stimulating factor induced Zn sequestration enhances macrophage superoxide and limits intracellular pathogen survival. Immunity. 2013;39(4):697–710. doi: 10.1016/j.immuni.2013.09.006 24138881.

43. Hovius JWR, de Jong MAWP, den Dunnen J, Litjens M, Fikrig E, van der Poll T, et al. Salp15 binding to DC-SIGN inhibits cytokine expression by impairing both nucleosome remodeling and mRNA stabilization. PLoS Pathog. 2008;4(2):e31. doi: 10.1371/journal.ppat.0040031 18282094.

44. Dillon S, Agrawal S, Banerjee K, Letterio J, Denning TL, Oswald-Richter K, et al. Yeast zymosan, a stimulus for TLR2 and dectin-1, induces regulatory antigen-presenting cells and immunological tolerance. J Clin Invest. 2006;116(4):916–28. doi: 10.1172/jci27203 16543948.

45. Tassi I, Cella M, Castro I, Gilfillan S, Khan WN, Colonna M. Requirement of phospholipase C-gamma2 (PLCgamma2) for Dectin-1-induced antigen presentation and induction of TH1/TH17 polarization. Eur J Immunol. 2009;39(5):1369–78. doi: 10.1002/eji.200839313 19404984.

46. Toyotome T, Adachi Y, Watanabe A, Ochiai E, Ohno N, Kamei K. Activator protein 1 is triggered by Aspergillus fumigatus beta-glucans surface-exposed during specific growth stages. Microb Pathog. 2008;44(2):141–50. doi: 10.1016/j.micpath.2007.08.015 17928189.

47. Palanki MS. Inhibitors of AP-1 and NF-kappa B mediated transcriptional activation: therapeutic potential in autoimmune diseases and structural diversity. Curr Med Chem. 2002;9(2):219–27. 11860356.

48. Shaulian E, Karin M. AP-1 as a regulator of cell life and death. Nat Cell Biol 2002;4(5):E131–6. doi: 10.1038/ncb0502-e131 11988758.

49. Ye N, Ding Y, Wild C, Shen Q, Zhou J. Small molecule inhibitors targeting activator protein 1 (AP-1). J Med Chem. 2014;57(16):6930–48. doi: 10.1021/jm5004733 24831826.

50. Prince JE, Brayton CF, Fossett MC, Durand JA, Kaplan SL, Smith CW, et al. The differential roles of LFA-1 and Mac-1 in host defense against systemic infection with Streptococcus pneumoniae. J Immunol. 2001;166(12):7362–9. 11390487.

51. Rijneveld AW, de Vos AF, Florquin S, Verbeek JS, van der Poll T. CD11b limits bacterial outgrowth and dissemination during murine pneumococcal pneumonia. J Infect Dis. 2005;191(10):1755–60. doi: 10.1086/429633 15838804.

52. Soloviev DA, Jawhara S, Fonzi WA. Regulation of innate immune response to Candida albicans infections by alphaMbeta2-Pra1p interaction. Infect Immun. 2011;79(4):1546–58. doi: 10.1128/iai.00650-10 21245270.

53. LeibundGut-Landmann S, Grosz O, Robinson MJ, Osorio F, Slack EC, Tsoni SV, 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(6):630–8. doi: 10.1038/ni1460 17450144.

54. Leibundgut-Landmann S, Osorio F, Brown GD, Reis e Sousa C. Stimulation of dendritic cells via the dectin-1/Syk pathway allows priming of cytotoxic T-cell responses. Blood. 2008;112(13):4971–80. doi: 10.1182/blood-2008-05-158469 18818389.

55. Gresnigt MS, Becker KL, Smeekens SP, Jacobs CW, Joosten LA, van der Meer JW, et al. Aspergillus fumigatus-induced IL-22 is not restricted to a specific Th cell subset and is dependent on complement receptor 3. J Immunol. 2013;190(11):5629–39. doi: 10.4049/jimmunol.1202601 23645883.

56. Lin JS, Wu-Hsieh BA. Functional T cells in primary immune response to histoplasmosis. Int Immunol. 2004;16(11):1663–73. doi: 10.1093/intimm/dxh168 15452021.

57. Deepe GS Jr., Gibbons RS. Interleukins 17 and 23 influence the host response to Histoplasma capsulatum. J Infec Dis. 2009;200(1):142–51. doi: 10.1086/599333 19469707.

58. Clemons KV, Darbonne WC, Curnutte JT, Sobel RA, Stevens DA. Experimental histoplasmosis in mice treated with anti-murine interferon-gamma antibody and in interferon-gamma gene knockout mice. Microbes Infect. 2000;2(9):997–1001. 10967280.

59. Allendoerfer R, Deepe GS Jr. Intrapulmonary response to Histoplasma capsulatum in gamma interferon knockout mice. Infect Immun. 1997;65(7):2564–9. 9199420.

60. Zhou P, Miller G, Seder RA. Factors involved in regulating primary and secondary immunity to infection with Histoplasma capsulatum: TNF-α plays a critical role in maintaining secondary immunity in the absence of IFN-γ. J Immunol. 1998;160(3):1359–68. 9570555.

61. Romani L, Mencacci A, Cenci E, Spaccapelo R, Toniatti C, Puccetti P, et al. Impaired neutrophil response and CD4+ T helper cell 1 development in interleukin 6-deficient mice infected with Candida albicans. J Exp Med. 1996;183(4):1345–55. 8666893.

62. Cenci E, Mencacci A, Casagrande A, Mosci P, Bistoni F, Romani L. Impaired antifungal effector activity but not inflammatory cell recruitment in interleukin-6-deficient mice with invasive pulmonary aspergillosis. J Infec Dis. 2001;184(5):610–7. doi: 10.1086/322793 11494166.

63. Taylor PR, Tsoni SV, Willment JA, Dennehy KM, Rosas M, Findon H, et al. Dectin-1 is required for beta-glucan recognition and control of fungal infection. Nat Immunol. 2007;8(1):31–8. doi: 10.1038/ni1408 17159984.

64. Cheng AM, Rowley B, Pao W, Hayday A, Bolen JB, Pawson T. Syk tyrosine kinase required for mouse viability and B-cell development. Nature. 1995;378(6554):303–6. doi: 10.1038/378303a0 7477353.

65. Yanagi S, Inatome R, Ding J, Kitaguchi H, Tybulewicz VLJ, Yamamura H. Syk expression in endothelial cells and their morphologic defects in embryonic Syk-deficient mice. Blood. 2001;98(9):2869–71. doi: 10.1182/blood.V98.9.2869 11675365.

66. Chow CW, Downey GP, Grinstein S. Measurements of phagocytosis and phagosomal maturation. Curr Protoc Cell Biol. 2004;Chapter 15:Unit 15.7. doi: 10.1002/0471143030.cb1507s22 18228442.

67. Newman SL, Mikus LK. Deposition of C3b and iC3b onto particulate activators of the human complement system. Quantitation with monoclonal antibodies to human C3. J Exp Med. 1985;161(6):1414–31. 2409200.

68. Ciaccio MF, Wagner JP, Chuu C-P, Lauffenburger DA, Jones RB. Systems analysis of EGF receptor signaling dynamics with microwestern arrays. Nat Methods. 2010;7(2):148–55. doi: 10.1038/nmeth.1418 20101245.