Role of innate cytokines in mycobacterial infection

Mucosal Immunology

Volumn 4, Issue 3, 2011, Pages 252-260

  Cooper, A M ^a   Mayer Barber, K D ^b   Sher, A ^b  

^a TRUDEAU INSTITUTE   (United States)

^b NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

GAMMA INTERFERON; ICOSANOID; INTERFERON; INTERLEUKIN 1; INTERLEUKIN 10; INTERLEUKIN 12; INTERLEUKIN 17; INTERLEUKIN 23; INTERLEUKIN 27; INTERLEUKIN 6; LYMPHOTOXIN; TUMOR NECROSIS FACTOR;

ADAPTIVE IMMUNITY; BACTERIAL VIRULENCE; CELLULAR IMMUNITY; CYTOKINE PRODUCTION; CYTOKINE RESPONSE; HOST PATHOGEN INTERACTION; HOST RESISTANCE; HUMAN; IMMUNOMODULATION; IMMUNOREGULATION; INNATE IMMUNITY; MYCOBACTERIOSIS; MYCOBACTERIUM TUBERCULOSIS; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; REVIEW;

EID: 79955110091     PISSN: 19330219     EISSN: None     Source Type: Journal    
DOI: 10.1038/mi.2011.13     Document Type: Review

References (102)

1. Cooper, A.M. & Khader, S.A. The role of cytokines in the initiation, expansion, and control of cellular immunity to tuberculosis. Immunol. Rev. 226, 191-204(2008).
2. Harris, J. & Keane, J. How tumour necrosis factor blockers interfere with tuberculosis immunity. Clin. Exp. Immunol. 161, 1-9 (2010).
3. Zhang, S. et al. Inborn errors of interferon (IFN)-mediated immunity in humans: insights into the respective roles of IFN-alpha/beta, IFN-gamma, and IFN-lambda in host defense. Immunol. Rev. 226, 29-40 (2008).
4. Grange, J.M., Bottasso, O., Stanford, C.A. & Stanford, J.L. Theuse of mycobacterial adjuvant-based agents for immunotherapy of cancer. Vaccine 26, 4984-4990 (2008).
5. Freund, J. et al. Antibody formation and sensitization with the aid of adjuvants. J. Immunol. 60, 383-398 (1948).
6. Alexandroff, A.B., Nicholson, S., Patel, P.M. & Jackson, A.M. Recent advances in bacillus Calmette-Guerin immunotherapy in bladder cancer. Immunotherapy 2, 551-560 (2010).
7. Filipe-Santos, O. et al. Inborn errors of IL-12/23- and IFN-gamma-mediated immunity: molecular, cellular, and clinical features. Semin. Immunol. 18, 347-361 (2006). (Pubitemid 44540199)
8. Trinchieri, G., Fflanz, S. & Kastelein, R. The IL-12 family of heterodimeric cytokines: new players in the regulation of T cell responses. Immunity 19, 641-644(2003). (Pubitemid 37490789)
9. Bafica, A., Scanga, C., Feng, C., Leifer, C., Cheever, A. & Sher, A. TLR9 regulates Th1 responses and cooperates with TLR2 in mediating optimal resistance to Mycobacterium tuberculosis. J. Exp. Med. 202, 1715-1724(2005). (Pubitemid 41815877)
10. Khader, S. et al. Interleukin 12p40 is required for dendritic cell migration and T cell priming after Mycobacterium tuberculosis infection. J. Exp. Med. 203, 1805-1815 (2006). (Pubitemid 44036285)
11. Robinson, R. et al. Mycobacterium tuberculosis infection induces ill 2rb1 splicing to generate a novel IL-12R|31 isoform that enhances DC migration. J. Exp. Med. 207, 591-605 (2010).
12. Holscher, C. et al. A protective and agonistic function of IL-12p40 in mycobacterial infection. J. Immunol. 167, 6957-6966 (2001). (Pubitemid 33144190)
13. Walter, M., Kajiawara, N., Karanja, P., Castro, M. & Holtzman, M.J. Interleukin-12 p40 production by barrier epithelial cells during airway inflammation. J. Exp. Med. 193, 339-351 (2001). (Pubitemid 32524517)
14. Altare, F et al. Impairment of mycobacterial immunity in human interleukin-12 receptor deficiency. Science 280, 1432-1435 (1998). (Pubitemid 28264836)
15. Gerosa, F et al. Differential regulation of interleukin 12 and interleukin 23 production in human dendritic cells. J. Exp. Med. 205, 1447-1461 (2008). (Pubitemid 351831499)
16. Silver, R. et al. Human alveolar macrophage gene responses to Mycobacterium tuberculosis strains H37Ra and H37Rv Am. J. Respir. Cell Mol. Biol. 40, 491-504 (2009).
17. Cooper, A.M., Kipnis, A., Turner, J., Magram, J., Ferrante, J. & Orme, I.M. Mice lacking bioactive IL-12 can generate protective, antigen-specific cellular responses to mycobacterial infection only if the IL-12 p40 subunit is present. J. Immunol. 168, 1322-1327 (2002). (Pubitemid 34094502)
18. Khader, S. et al. IL-23 compensates for the absence of IL-12p70 and is essential for the IL-17 response during tuberculosis but is dispensable for protection and antigen-specific IFN-gamma responses if IL-12p70 is available. J. Immunol. 175, 788-795 (2005). (Pubitemid 41094960)
19. Feng, C. et al. Maintenance of pulmonary Th1 effector function in chronic tuberculosis requires persistent IL-12 production. J. Immunol. 174, 4185-4192(2005). (Pubitemid 40395997)
20. Riol-Blanco, L. et al. IL-23 receptor regulates unconventional IL-17-producing T cells that control bacterial infections. J. Immunol. 184, 1710-1720(2010).
21. Umemura, M. et al. IL-17-mediated regulation of innate and acquired immune response against pulmonary Mycobacterium bovis bacille Calmette-Guerin infection. J. Immunol. 178, 3786-3796 (2007). (Pubitemid 46417647)
22. Okamoto Yoshida, Y. et al. Essential role of IL-17A in the formation of a mycobacterial infection-induced granuloma in the lung. J. Immunol. 184, 4414-4422(2010).
23. Lockhart, E., Green, A. & Flynn, J. IL-17 production is dominated by gammadelta T cells rather than CD4 T cells during Mycobacterium tuberculosis infection. J. Immunol. 177, 4662-4669 (2006). (Pubitemid 44469799)
24. Koch, R. Fortsetzung der mittheilung uber ein heilmittel gegen tuberkulose. Dtsch. Med. Wochenschr. 17, 101 (1891).
25. Cruz, A. et al. Pathological role of Interleukin 17 in mice subjected to repeated BCG vaccination after infection with Mycobacterium tuberculosis. J. Exp. Med. 207, 1609-1616 (2010).
26. Verreck, F.A.W. et al. Human IL-23-producingtype 1 macrophages promote but IL-10-producing type 2 macrophages subvert immunity to (myco)bacteria. Proc. Natl Acad. Sci. USA 101, 4560-4565 (2004). (Pubitemid 38437450)
27. Juffermans, N.P. et al. Interleukin-1 signaling is essential for host defense during murine pulmonary tuberculosis. J. Infect. Dis. 182, 902-908 (2000).
28. Sugawara, I., Yamada, H., Hua, S. & Mizuno, S. Role of interleukin (IL)-1 type 1 receptor in mycobacterial infection. Microbiol. Immunol. 45, 743-750(2001). (Pubitemid 33111351)
29. Sugawara, I., Yamada, H, Kaneko, H, Mizuno, S., Takeda, K. & Akira, S. Role of interleukin-18 (IL-18) in mycobacterial infection in IL-18-gene-disrupted mice. Infect. Immunol. 67, 2585-2589 (1999). (Pubitemid 29200522)
30. Yamada, H., Mizumo, S., Horai, R., Iwakura, Y. & Sugawara, I. Protective role of interleukin-1 in mycobacterial infection in IL-1 alpha/beta double-knockout mice. Lab. Invest. 80, 759-767 (2000). (Pubitemid 30340660)
31. Sugawara, I., Yamada, H., Mizuno, S., Takeda, K. & Akira, S. Mycobacterial infection in MyD88-deficient mice. Microbiol. Immunol. 47, 841-847(2003). (Pubitemid 37433018)
32. Scanga, C., Bafica, A., Feng, C., Cheever, A., Hieny S. & Sher, A. MyD88-deficient mice display a profound loss in resistance to Mycobacterium tuberculosis associated with partially impaired Th1 cytokine and nitric oxide synthase 2 expression. Infect. Immunol. 72, 2400-2404 (2004). (Pubitemid 38419959)
33. Feng, C. et al. Mice lacking myeloid differentiation factor 88 display profound defects in host resistance and immune responses to Mycobacterium avium infection not exhibited by Toll-like receptor 2 (TLR2)- and TLR4-deficient animals. J. Immunol. 171, 4758-4764 (2003). (Pubitemid 37310594)
34. Fremond, C., Yeremeev, V, Nicolle, D., Jacobs, M., Quesniaux, V & Ryffel, B. Fatal Mycobacterium tuberculosis infection despite adaptive immune response in the absence of MyD88. J. Clin. Invest. 114, 1790-1799(2004). (Pubitemid 40385535)
35. Fremond, CM. et al. IL-1 receptor-mediated signal is an essential component of MyD88-dependent innate response to Mycobacterium tuberculosis infection. J. Immunol. 179, 1178-1189 (2007).
36. Mayer-Barber, K.D. et al. Cutting edge: caspase-1 independent IL-1 {beta} production is critical for host resistance to Mycobacterium tuberculosis and does not require TLR signaling in vivo. J Immunol. 184, 3326-3330(2010).
37. Walter, K., Holscher, C., Tschopp, J. & Ehlers, S. NALP3 is not necessary for early protection against experimental tuberculosis. Immunobiology 215, 804-811 (2010).
38. Kinjo, Y. et al. Contribution of IL-18 to Th1 response and host defense against infection by Mycobacterium tuberculosis. J. Immunol. 169, 323-329 (2002). (Pubitemid 34686152)
39. Schneider, B.E. et al. A role for IL-18 in protective immunity against Mycobacterium tuberculosis. Eur. J. Immunol. 40, 396-405 (2010).
40. Korbel, D.S., Schneider, B.E. & Schaible, U.E. Innate immunity in tuberculosis: myths and truth. Microbes Infect. 10, 995-1004 (2008).
41. Wieland, C.W., van der Windt, G.J., Florquin, S., McKenzie, A.N. & van der Poll, T. ST2 deficient mice display a normal host defense against pulmonary infection with Mycobacterium tuberculosis. Microbes Infect. 11, 524-530(2009).
42. Dinarello, C.A. Immunological and inflammatory functions of the interleukin-1 family. Annu. Rev. Immunol. 27, 519-550 (2009).
43. McElvania Tekippe, E. et al. Granuloma formation and host defense in chronic Mycobacterium tuberculosis infection requires PYCARD/ASC but not NLRP3 or caspase-1. PLoS One 5, e12320 (2010).
44. Koo, I.C., Wang, C., Raghavan, S., Morisaki, J.H., Cox, J.S. & Brown, E.J. ESX-1 -dependent cytolysis in lysosome secretion and inflammasome activation during mycobacterial infection. Cell Microbiol. 10, 1866-1878(2008).
45. Greten, FR. et al. NF-kappaB is a negative regulator of IL-1 beta secretion as revealed by genetic and pharmacological inhibition of IKKbeta. Cell 130, 918-931 (2007). (Pubitemid 47332565)
46. Bellamy, R., Ruwende, C., Corrah, T., McAdam, K.P.W.J., Whittle, H.C. & Hill, A.V. Assessment of the interleukin-1 gene cluster and other candidate gene polymorphisms in host susceptibility to tuberculosis. Tuberc. Lung Dis. 79, 83-89 (1998). (Pubitemid 29078276)
47. Gomez, L.M., Camargo, J.F., Castiblanco, J., Ruiz-Narvaez, E.A., Cadena, J. & Anaya, J.M. Analysis of IL1B, TAP1, TAP2 and IKBL polymorphisms on susceptibility to tuberculosis. Tissue Antigens 67, 290-296 (2006).
48. Awomoyi, A.A. et al. Polymorphism in IL1B: IL1B-511 association with tuberculosis and decreased lipopolysaccharide-induced IL-1 beta in IFN-gamma primed ex-vivo whole blood assay. J. Endotoxin. Res. 11, 281-286(2005). (Pubitemid 41556035)
49. Wilkinson, R.J. et al. Influence of polymorphism in the genes for the interleukin (IL)-1 receptor antagonist and IL-1 beta on tuberculosis. J. Exp. Med. 189, 1863-1874 (1999).
50. Settas, L.D., Tsimirikas, G., Vosvotekas, G., Triantafyllidou, E. & Nicolaides, P. Reactivation of pulmonary tuberculosis in a patient with rheumatoid arthritis during treatment with IL-1 receptor antagonists (anakinra). J. Clin. Rheumatol. 13, 219-220 (2007). (Pubitemid 47364586)
51. Taylor, P. & Feldmann, M. Anti-TNF biologic agents: still the therapy of choice for rheumatoid arthritis. Nat. Rev. Rheumatol. 5, 578-582 (2009).
52. Feng, C.G. et al. NK cell-derived IFN-gamma differentially regulates innate resistance and neutrophil response in T cell-deficient hosts infected with Mycobacterium tuberculosis. J. Immunol. 177, 7086-7093 (2006). (Pubitemid 44715076)
53. Junqueira-Kipnis, A. P. et al. NK cells respond to pulmonary infection with Mycobacterium tuberculosis, but play a minimal role in protection. J. Immunol. 171, 6039-6045 (2003). (Pubitemid 37467223)
54. Denis, M. Recombinant murine beta interferon enhances resistance of mice to systemic Mycobacterium avium infection. Infect. Immunol. 59, 1857-1859(1991).
55. Manca, C. et al. Virulence of a Mycobacterium tuberculosis clinical isolate in mice is determined by failure to induce Th1 type immunity and is associated with induction of IFN-alpha/beta. Proc. Natl Acad. Sci. USA 98, 5752-5757 (2001). (Pubitemid 32435714)
56. Manca, C. et al. Hypervirulent M. tuberculosis W/Beijing strains upregulate type I IFNs and increase expression of negative regulators of the Jak-Stat pathway. J. Interferon Cytokine Res. 25, 694-701 (2005). (Pubitemid 43010524)
57. Ordway D. et al. The hypervirulent Mycobacterium tuberculosis strain HN878 induces a potent TH1 response followed by rapid down-regulation. J. Immunol. 179, 522-531 (2007). (Pubitemid 46986569)
58. Antonelli, L.R. et al. Intranasal Poly-IC treatment exacerbates tuberculosis in mice through the pulmonary recruitment of a pathogen-permissive monocyte/macrophage population. J. Clin. Invest. 120, 1674-1682(2010).
59. O'Connell, R.M. et al. Type I interferon production enhances susceptibility to Listeria monocytogenes infection. J. Exp. Med. 200, 437-445 (2004). (Pubitemid 39121901)
60. Stanley, S.A., Johndrow, J.E., Manzanillo, P. & Cox, J.S. The type IIFN response to infection with Mycobacterium tuberculosis requires ESX-1-mediated secretion and contributes to pathogenesis. J. Immunol. 178, 3143-3152(2007). (Pubitemid 46333196)
61. Pandey A. K. et al. NOD2, RIP2 and IRF5 play a critical role in the type I interferon response to Mycobacterium tuberculosis. PLoS Pathog. 5, e1000500 (2009).
62. Berry, M.P. et al. An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis. Nature 466, 973-977 (2010).
63. Kastelein, R., Hunter, C. & Cua, D. Discovery and biology of IL-23 and IL-27: related but functionally distinct regulators of inflammation. Annu. Rev. Immunol. 25, 221-242 (2007). (Pubitemid 46697908)
64. Barnes, P.F., Lu, S., Abrams, J.S., Wang, E., Yamamura, M. & Modlin, R.L. Cytokine production at the site of disease in human tuberculosis. Infect. Immunol. 61, 3482-3489 (1993). (Pubitemid 23223442)
65. Awomoyi, A., Marchant, A., Howson, J., McAdam, K., Blackwell, J. & Newport, M. Interleukin-10, polymorphism in SLC11A1 (formerly NRAMP1), and susceptibility to tuberculosis. J. Inf. Dis. 186, 1808-1814 (2002). (Pubitemid 35463514)
66. Turner, J. et al. In vivo IL-10 production reactivates chronic pulmonary tuberculosis in C57BL/6 mice. J. Immunol. 169, 6343-6351 (2002). (Pubitemid 36903482)
67. Beamer, G. et al. Interleukin-10 promotes Mycobacterium tuberculosis disease progression in CBA/J mice. J. Immunol. 181, 5545-5550 (2008).
68. O'Leary, S., O'Sullivan, M. & Keane, J. IL-10 blocks phagosome maturation in Mycobacterium tuberculosis-Infected human macrophages. Am. J. Respir. Cell Mol. Biol., e-pub ahead of print 11 February 2011 doi:10.1165/rcmb.2010-03190c.
69. Higgins, D., Sanchez-Campillo, J., Rosas-Taraco, A., Lee, E., Orme, I. & Gonzalez-Juarrero, M. Lack of IL-10 alters inflammatory and immune responses during pulmonary Mycobacterium tuberculosis infection. Tuberculosis (Edinb) 89, 149-157 (2009).
70. Saunders, B., Frank, A., Orme, I. & Cooper, A. Interleukin-6 induces early gamma interferon production in the infected lung but is not required for generation of specific immunity to Mycobacterium tuberculosis infection. Infect. Immunol. 68, 3322-3326 (2000). (Pubitemid 30340426)
71. Appelberg, R., Castro, A.G., Pedrosa, J. & Minoprio, P. Role of interleukin-6 in the induction of protective T cells during mycobacterial infections in mice. Immunology 82, 361-364 (1994). (Pubitemid 24251616)
72. Leal, I.S., Smedegard, B., Andersen, P. & Appelberg, R. Interleukin-6 and interleukin-12 participate in induction of a type 1 protective T-cell response during vaccination with a tuberculosis subunit vaccine. Infect. Immunol. 67, 5747-5754 (1999). (Pubitemid 29508094)
73. Ladel, C.H., Blum, C., Dreher, A., Reifenberg, K., Kopf, M. & Kaufmann, S.H.E. Lethal tuberculosis in interleukin-6-deficient mice. Infect. Immunol. 65, 4843-4849 (1997).
74. Jones, G. et al. Loss of CD4+ T cell IL-6R expression during inflammation underlines a role for IL-6 trans signaling in the local maintenance of Th17 cells. J. Immunol. 184, 2130-2139 (2010).
75. Sodenkamp, J., Behrends, J., Förster, I., Müllen W, Ehlers, S. & Hölscher, C. gp130 on macrophages/granulocytes modulates inflammation during experimental tuberculosis. Eur. J. Cell Biol, e-pub ahead of print 6 December 2010 dx.doi.org/10.1016/j.ejcb.2010.10.010.
76. Pearl, J.E. et al. IL-27 signaling compromises control of bacterial growth in mycobacteria-infected mice. J. Immunol. 173, 7490-7496 (2004). (Pubitemid 39628189)
77. Holscher, C. et al. The IL-27 receptor chain WSX-1 differentially regulates antibacterial immunity and survival during experimental tuberculosis. J. Immunol. 174, 3534-3544 (2005). (Pubitemid 40354062)
78. Stumhofer, J. et al. Interleukin 27 negatively regulates the development of interleukin 17-producing T helper cells during chronic inflammation of the central nervous system. Nat. Immunol. 7, 937-945 (2006). (Pubitemid 44263907)
79. Stumhofer, J. et al. Interleukins 27 and 6 induce STAT3-mediated T cell production of interleukin 10. Nat. Immunol. 8, 1363-1371 (2007). (Pubitemid 350131173)
80. Stumhofer, J. et al. A role for IL-27p28 as an antagonist of gp130-mediated signaling. Nat. Immunol. 11, 1119-1126 (2010).
81. Flynn, J.L. et al. Tumor necrosis factor-alpha is required in the protective immune response against Mycobacterium tuberculosis in mice. Immunity 2, 561-572 (1995).
82. Roach, D., Bean, A., Demangel, C., France, M., Briscoe, H. & Britton, W. TNF regulates chemokine induction essential for cell recruitment, granuloma formation, and clearance of mycobacterial infection. J. Immunol. 168, 4620-4627 (2002). (Pubitemid 34441368)
83. Saunders, B., Tran, S., Ruuls, S., Sedgwick, J., Briscoe, H. & Britton, W. Transmembrane TNF is sufficient to initiate cell migration and granuloma formation and provide acute, but not long-term, control of Mycobacterium tuberculosis infection. J. Immunol. 174, 4852-4859 (2005).
84. Olleros, M. et al. Contribution of transmembrane tumor necrosis factor to host defense against Mycobacterium bovis bacillus Calmette-guerin and Mycobacterium tuberculosis infections. Am. J. Path. 166, 1109-1120 (2005). (Pubitemid 40524435)
85. Roach, D., Briscoe, H., Saunders, B., France, M., Riminton, S. & Britton, W. Secreted lymphotoxin - a is essential for the control of an intracellular bacterial infection. J. Exp. Med. 193, 239-246 (2001). (Pubitemid 32524455)
86. Ehlers, S. et al. The lymphotoxin beta receptor is critically involved in controlling infections with the intracellular pathogens Mycobacterium tuberculosis and Listeria monocytogenes. J. Immunol. 170, 5210-5218 (2003). (Pubitemid 36554754)
87. Allie, N. et al. Limited role for lymphotoxin a in the host immune response to Mycobacterium tuberculosis. J. Immunol. 185, 4292-4301 (2010).
88. Hagge, D. et al. Lymphotoxin-alpha and TNF have essential but independent roles in the evolution of the granulomatous response in experimental leprosy. Am. J. Path. 174, 1379-1389 (2009).
89. Divangahi, M., Desjardins, D., Nunes-Alves, C., Remold, H.G. & Behar, S.M. Eicosanoid pathways regulate adaptive immunity to Mycobacterium tuberculosis. Nat. Immunol. 11, 751-758 (2010).
90. Bafica, A. et al. Host control of Mycobacterium tuberculosis is regulated by 5-lipoxygenase-dependent lipoxin production. J. Clin. Invest. 115, 1601-1606(2005). (Pubitemid 40814668)
91. Chen, M. et al. Lipid mediators in innate immunity against tuberculosis: opposing roles of PGE2 and LXA4 in the induction of macrophage death. J. Exp. Med. 205, 2791-2801 (2008).
92. Behar, S.M., Divangahi, M. & Remold, H.G. Evasion of innate immunity by Mycobacterium tuberculosis: is death an exit strategy? Nat. Rev. Microbiol. 8, 668-674 (2010).
93. Tobin, D.M. et al. Thelta4h locus modulates susceptibility to mycobacterial infection in zebrafish and humans. Cell 140, 717-730 (2010).
94. Gagneux, S. et al. Variable host-pathogen compatibility in Mycobacterium tuberculosis. Proc. Natl Acad. Sci. USA 103, 2869-2873 (2006).
95. Reed, M. et al. A glycolipid of hypervirulent tuberculosis strains that inhibits the innate immune response. Nature 431, 84-87 (2004). (Pubitemid 39215112)
96. Wang, C. et al. Innate immune response to Mycobacterium tuberculosis Beijing and other genotypes. PLoS One 25, e13594 (2010).
97. Intemann, C. et al. Autophagy gene variant IRGM -261T contributes to protection from tuberculosis caused by Mycobacterium tuberculosis but not by M. africanum strains. PLoS Pathog. 5, e1000577 (2009).
98. Glickman, M., Cox, J. & Jacobs, W. A novel mycolic acid synthetase is required for cording, persistence and virulence of Mycobacterium tuberculosis. Mol. Cell 5, 717-727 (2000).
99. Rao, V., Gao, F., Chen, B., Jacobs, W.J. & Glickman, M. Trans-cyclopropanation of mycolic acids on trehalose dimycolate suppresses Mycobacterium tuberculosis-induced inflammation and virulence. J. Clin. Invest. 116, 1660-1667 (2006).
100. Schoenen, H. et al. Cutting edge: Mincle is essential for recognition and adjuvanticity of the mycobacterial cord factor and its synthetic analog trehalose-dibehenate. J. Immunol. 184, 2756-2760 (2010).
101. Werninghaus, K. et al. Adjuvanticity of a synthetic cord factor analogue for subunit Mycobacterium tuberculosis vaccination requires FcRgamma-Syk-Card9- dependent innate immune activation. J. Exp. Med. 206, 89-97 (2009).
102. Ishikawa, E. et al. Direct recognition of the mycobacterial glycolipid, trehalose dimycolate, by C-type lectin Mincle. J. Exp. Med. 206, 2879-2888 (2009).