Toll-like Receptors and Their Crosstalk with Other Innate Receptors in Infection and Immunity

Immunity

Volumn 34, Issue 5, 2011, Pages 637-650

  Kawai, Taro ^a,b   Akira, Shizuo ^a,b  

^a OSAKA UNIVERSITY   (Japan)

^b OSAKA UNIVERSITY   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

LECTIN RECEPTOR; NUCLEOTIDE BINDING OLIGOMERIZATION DOMAIN LIKE RECEPTOR; PATTERN RECOGNITION RECEPTOR; RETINOIC ACID INDUCIBLE PROTEIN I; RIG I LIKE RECEPTOR; TOLL LIKE RECEPTOR; UNCLASSIFIED DRUG;

ANTIGEN RECOGNITION; HUMAN; INFECTION; INNATE IMMUNITY; MOLECULAR INTERACTION; NONHUMAN; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN FUNCTION; REVIEW;

ANIMALS; HUMANS; IMMUNITY, INNATE; INFECTION; PROTEIN TRANSPORT; RECEPTORS, IMMUNOLOGIC; SIGNAL TRANSDUCTION; TOLL-LIKE RECEPTORS;

EID: 79956300649     PISSN: 10747613     EISSN: 10974180     Source Type: Journal    
DOI: 10.1016/j.immuni.2011.05.006     Document Type: Review

References (131)

1. Adachi K., Tsutsui H., Kashiwamura S., Seki E., Nakano H., Takeuchi O., Takeda K., Okumura K., Van Kaer L., Okamura H., et al. Plasmodium berghei infection in mice induces liver injury by an IL-12- and toll-like receptor/myeloid differentiation factor 88-dependent mechanism. J. Immunol. 2001, 167:5928-5934.
2. Akira S., Uematsu S., Takeuchi O. Pathogen recognition and innate immunity. Cell 2006, 124:783-801.
3. Andersen-Nissen E., Hawn T.R., Smith K.D., Nachman A., Lampano A.E., Uematsu S., Akira S., Aderem A. Cutting edge: Tlr5-/- mice are more susceptible to Escherichia coli urinary tract infection. J. Immunol. 2007, 178:4717-4720.
4. Arpaia N., Godec J., Lau L., Sivick K.E., McLaughlin L.M., Jones M.B., Dracheva T., Peterson S.N., Monack D.M., Barton G.M. TLR signaling is required for Salmonella typhimurium virulence. Cell 2011, 144:675-688.
5. Bafica A., Santiago H.C., Goldszmid R., Ropert C., Gazzinelli R.T., Sher A. Cutting edge: TLR9 and TLR2 signaling together account for MyD88-dependent control of parasitemia in Trypanosoma cruzi infection. J. Immunol. 2006, 177:3515-3519.
6. Barbalat R., Lau L., Locksley R.M., Barton G.M. Toll-like receptor 2 on inflammatory monocytes induces type I interferon in response to viral but not bacterial ligands. Nat. Immunol. 2009, 10:1200-1207.
7. Barbalat R., Ewald S.E., Mouchess M.L., Barton G.M. Nucleic acid recognition by the innate immune system. Annu. Rev. Immunol. 2011, 29:185-214.
8. Barber G.N. Innate immune DNA sensing pathways: STING, AIMII and the regulation of interferon production and inflammatory responses. Curr. Opin. Immunol. 2011, 23:10-20.
9. Barton G.M., Kagan J.C. A cell biological view of Toll-like receptor function: regulation through compartmentalization. Nat. Rev. Immunol. 2009, 9:535-542.
10. Bellocchio S., Montagnoli C., Bozza S., Gaziano R., Rossi G., Mambula S.S., Vecchi A., Mantovani A., Levitz S.M., Romani L. The contribution of the Toll-like/IL-1 receptor superfamily to innate and adaptive immunity to fungal pathogens in vivo. J. Immunol. 2004, 172:3059-3069.
11. Beutler B.A. TLRs and innate immunity. Blood 2009, 113:1399-1407.
12. Biondo C., Signorino G., Costa A., Midiri A., Gerace E., Galbo R., Bellantoni A., Malara A., Beninati C., Teti G., Mancuso G. Recognition of yeast nucleic acids triggers a host protective type I interferon response. Eur. J. Immunol. 2011, in press. Published online April 11, 2011.
13. Blasius A.L., Beutler B. Intracellular toll-like receptors. Immunity 2010, 32:305-315.
14. Bourgeois C., Majer O., Frohner I.E., Lesiak-Markowicz I., Hildering K.S., Glaser W., Stockinger S., Decker T., Akira S., Müller M., Kuchler K. Conventional dendritic cells mount a type I IFN response against Candida spp. requiring novel phagosomal TLR7-mediated IFN-beta signaling. J. Immunol. 2011, 186:3104-3112.
15. Bozza S., Gaziano R., Lipford G.B., Montagnoli C., Bacci A., Di Francesco P., Kurup V.P., Wagner H., Romani L. Vaccination of mice against invasive aspergillosis with recombinant Aspergillus proteins and CpG oligodeoxynucleotides as adjuvants. Microbes Infect. 2002, 4:1281-1290.
16. Brinkmann M.M., Spooner E., Hoebe K., Beutler B., Ploegh H.L., Kim Y.M. The interaction between the ER membrane protein UNC93B and TLR3, 7, and 9 is crucial for TLR signaling. J. Cell Biol. 2007, 177:265-275.
17. Casanova J.L., Abel L., Quintana-Murci L. Human TLRs and IL-1Rs in host defense: Natural insights from evolutionary, epidemiological, and clinical genetics. Annu. Rev. Immunol. 2011, 29:447-491.
18. Casrouge A., Zhang S.Y., Eidenschenk C., Jouanguy E., Puel A., Yang K., Alcais A., Picard C., Mahfoufi N., Nicolas N., et al. Herpes simplex virus encephalitis in human UNC-93B deficiency. Science 2006, 314:308-312.
19. Choi Y.J., Im E., Chung H.K., Pothoulakis C., Rhee S.H. TRIF mediates Toll-like receptor 5-induced signaling in intestinal epithelial cells. J. Biol. Chem. 2010, 285:37570-37578.
20. Coban C., Ishii K.J., Kawai T., Hemmi H., Sato S., Uematsu S., Yamamoto M., Takeuchi O., Itagaki S., Kumar N., et al. Toll-like receptor 9 mediates innate immune activation by the malaria pigment hemozoin. J. Exp. Med. 2005, 201:19-25.
21. Coban C., Ishii K.J., Uematsu S., Arisue N., Sato S., Yamamoto M., Kawai T., Takeuchi O., Hisaeda H., Horii T., Akira S. Pathological role of Toll-like receptor signaling in cerebral malaria. Int. Immunol. 2007, 19:67-79.
22. Coban C., Igari Y., Yagi M., Reimer T., Koyama S., Aoshi T., Ohata K., Tsukui T., Takeshita F., Sakurai K., et al. Immunogenicity of whole-parasite vaccines against Plasmodium falciparum involves malarial hemozoin and host TLR9. Cell Host Microbe 2010, 7:50-61.
23. Daffis S., Samuel M.A., Suthar M.S., Gale M., Diamond M.S. Toll-like receptor 3 has a protective role against West Nile virus infection. J. Virol. 2008, 82:10349-10358.
24. Dorhoi A., Desel C., Yeremeev V., Pradl L., Brinkmann V., Mollenkopf H.J., Hanke K., Gross O., Ruland J., Kaufmann S.H. The adaptor molecule CARD9 is essential for tuberculosis control. J. Exp. Med. 2010, 207:777-792.
25. Dostert C., Guarda G., Romero J.F., Menu P., Gross O., Tardivel A., Suva M.L., Stehle J.C., Kopf M., Stamenkovic I., et al. Malarial hemozoin is a Nalp3 inflammasome activating danger signal. PLoS ONE 2009, 4:e6510.
26. Edelmann K.H., Richardson-Burns S., Alexopoulou L., Tyler K.L., Flavell R.A., Oldstone M.B. Does Toll-like receptor 3 play a biological role in virus infections?. Virology 2004, 322:231-238.
27. Edwards A.D., Diebold S.S., Slack E.M., Tomizawa H., Hemmi H., Kaisho T., Akira S., Reis e Sousa C. Toll-like receptor expression in murine DC subsets: lack of TLR7 expression by CD8 alpha+ DC correlates with unresponsiveness to imidazoquinolines. Eur. J. Immunol. 2003, 33:827-833.
28. Elinav E., Strowig T., Henao-Mejia J., Flavell R.A. Regulation of the antimicrobial response by NLR proteins. Immunity 2011, 34:665-679. this issue.
29. Ewald S.E., Engel A., Lee J., Wang M., Bogyo M., Barton G.M. Nucleic acid recognition by Toll-like receptors is coupled to stepwise processing by cathepsins and asparagine endopeptidase. J. Exp. Med. 2011, 208:643-651.
30. Fernandes-Alnemri T., Yu J.W., Juliana C., Solorzano L., Kang S., Wu J., Datta P., McCormick M., Huang L., McDermott E., et al. The AIM2 inflammasome is critical for innate immunity to Francisella tularensis. Nat. Immunol. 2010, 11:385-393.
31. Feuillet V., Medjane S., Mondor I., Demaria O., Pagni P.P., Galán J.E., Flavell R.A., Alexopoulou L. Involvement of Toll-like receptor 5 in the recognition of flagellated bacteria. Proc. Natl. Acad. Sci. USA 2006, 103:12487-12492.
32. Fremond C.M., Togbe D., Doz E., Rose S., Vasseur V., Maillet I., Jacobs M., Ryffel B., Quesniaux V.F. IL-1 receptor-mediated signal is an essential component of MyD88-dependent innate response to Mycobacterium tuberculosis infection. J. Immunol. 2007, 179:1178-1189.
33. Fukui R., Saitoh S., Matsumoto F., Kozuka-Hata H., Oyama M., Tabeta K., Beutler B., Miyake K. Unc93B1 biases Toll-like receptor responses to nucleic acid in dendritic cells toward DNA- but against RNA-sensing. J. Exp. Med. 2009, 206:1339-1350.
34. Gandotra S., Jang S., Murray P.J., Salgame P., Ehrt S. Nucleotide-binding oligomerization domain protein 2-deficient mice control infection with Mycobacterium tuberculosis. Infect. Immun. 2007, 75:5127-5134.
35. Gavin A.L., Hoebe K., Duong B., Ota T., Martin C., Beutler B., Nemazee D. Adjuvant-enhanced antibody responses in the absence of toll-like receptor signaling. Science 2006, 314:1936-1938.
36. Gazzinelli R.T., Denkers E.Y. Protozoan encounters with Toll-like receptor signalling pathways: Implications for host parasitism. Nat. Rev. Immunol. 2006, 6:895-906.
37. Geijtenbeek T.B., Gringhuis S.I. Signalling through C-type lectin receptors: Shaping immune responses. Nat. Rev. Immunol. 2009, 9:465-479.
38. Gerold G., Zychlinsky A., de Diego J.L. What is the role of Toll-like receptors in bacterial infections?. Semin. Immunol. 2007, 19:41-47.
39. Gilliet M., Cao W., Liu Y.J. Plasmacytoid dendritic cells: Sensing nucleic acids in viral infection and autoimmune diseases. Nat. Rev. Immunol. 2008, 8:594-606.
40. Glocker E.O., Hennigs A., Nabavi M., Schäffer A.A., Woellner C., Salzer U., Pfeifer D., Veelken H., Warnatz K., Tahami F., et al. A homozygous CARD9 mutation in a family with susceptibility to fungal infections. N. Engl. J. Med. 2009, 361:1727-1735.
41. Goodridge H.S., Underhill D.M. Fungal recognition by TLR2 and Dectin-1. Handb Exp Pharmacol 2008, 183:87-109.
42. Gotoh K., Tanaka Y., Nishikimi A., Nakamura R., Yamada H., Maeda N., Ishikawa T., Hoshino K., Uruno T., Cao Q., et al. Selective control of type I IFN induction by the Rac activator DOCK2 during TLR-mediated plasmacytoid dendritic cell activation. J. Exp. Med. 2010, 207:721-730.
43. Griffith J.W., Sun T., McIntosh M.T., Bucala R. Pure Hemozoin is inflammatory in vivo and activates the NALP3 inflammasome via release of uric acid. J. Immunol. 2009, 183:5208-5220.
44. Gross O., Gewies A., Finger K., Schäfer M., Sparwasser T., Peschel C., Förster I., Ruland J. Card9 controls a non-TLR signalling pathway for innate anti-fungal immunity. Nature 2006, 442:651-656.
45. Gross O., Poeck H., Bscheider M., Dostert C., Hannesschläger N., Endres S., Hartmann G., Tardivel A., Schweighoffer E., Tybulewicz V., et al. Syk kinase signalling couples to the Nlrp3 inflammasome for anti-fungal host defence. Nature 2009, 459:433-436.
46. Haas T., Metzger J., Schmitz F., Heit A., Müller T., Latz E., Wagner H. The DNA sugar backbone 2' deoxyribose determines toll-like receptor 9 activation. Immunity 2008, 28:315-323.
47. Hisaeda H., Tetsutani K., Imai T., Moriya C., Tu L., Hamano S., Duan X., Chou B., Ishida H., Aramaki A., et al. Malaria parasites require TLR9 signaling for immune evasion by activating regulatory T cells. J. Immunol. 2008, 180:2496-2503.
48. Hise A.G., Tomalka J., Ganesan S., Patel K., Hall B.A., Brown G.D., Fitzgerald K.A. An essential role for the NLRP3 inflammasome in host defense against the human fungal pathogen Candida albicans. Cell Host Microbe 2009, 5:487-497.
49. Hoffmann J.A. The immune response of Drosophila. Nature 2003, 426:33-38.
50. Hölscher C., Reiling N., Schaible U.E., Hölscher A., Bathmann C., Korbel D., Lenz I., Sonntag T., Kröger S., Akira S., et al. Containment of aerogenic Mycobacterium tuberculosis infection in mice does not require MyD88 adaptor function for TLR2, -4 and -9. Eur. J. Immunol. 2008, 38:680-694.
51. Honda K., Ohba Y., Yanai H., Negishi H., Mizutani T., Takaoka A., Taya C., Taniguchi T. Spatiotemporal regulation of MyD88-IRF-7 signalling for robust type-I interferon induction. Nature 2005, 434:1035-1040.
52. Horner S.M., Gale M. Intracellular innate immune cascades and interferon defenses that control hepatitis C virus. J. Interferon Cytokine Res. 2009, 29:489-498.
53. Hou B., Benson A., Kuzmich L., DeFranco A.L., Yarovinsky F. Critical coordination of innate immune defense against Toxoplasma gondii by dendritic cells responding via their Toll-like receptors. Proc. Natl. Acad. Sci. USA 2011, 108:278-283.
54. Husebye H., Aune M.H., Stenvik J., Samstad E., Skjeldal F., Halaas O., Nilsen N.J., Stenmark H., Latz E., Lien E., et al. The Rab11a GTPase controls Toll-like receptor 4-induced activation of interferon regulatory factor-3 on phagosomes. Immunity 2010, 33:583-596.
55. Ichinohe T. Respective roles of TLR, RIG-I and NLRP3 in influenza virus infection and immunity: Impact on vaccine design. Expert Rev. Vaccines 2010, 9:1315-1324.
56. Imai Y., Kuba K., Neely G.G., Yaghubian-Malhami R., Perkmann T., van Loo G., Ermolaeva M., Veldhuizen R., Leung Y.H., Wang H., et al. Identification of oxidative stress and Toll-like receptor 4 signaling as a key pathway of acute lung injury. Cell 2008, 133:235-249.
57. Ishii K.J., Kawagoe T., Koyama S., Matsui K., Kumar H., Kawai T., Uematsu S., Takeuchi O., Takeshita F., Coban C., Akira S. TANK-binding kinase-1 delineates innate and adaptive immune responses to DNA vaccines. Nature 2008, 451:725-729.
58. Ishikawa E., Ishikawa T., Morita Y.S., Toyonaga K., Yamada H., Takeuchi O., Kinoshita T., Akira S., Yoshikai Y., Yamasaki S. Direct recognition of the mycobacterial glycolipid, trehalose dimycolate, by C-type lectin Mincle. J. Exp. Med. 2009, 206:2879-2888.
59. Janeway C.A. Approaching the asymptote? Evolution and revolution in immunology. Cold Spring Harb. Symp. Quant. Biol. 1989, 54:1-13.
60. Joly S., Ma N., Sadler J.J., Soll D.R., Cassel S.L., Sutterwala F.S. Cutting edge: Candida albicans hyphae formation triggers activation of the Nlrp3 inflammasome. J. Immunol. 2009, 183:3578-3581.
61. Kanto T., Inoue M., Miyatake H., Sato A., Sakakibara M., Yakushijin T., Oki C., Itose I., Hiramatsu N., Takehara T., et al. Reduced numbers and impaired ability of myeloid and plasmacytoid dendritic cells to polarize T helper cells in chronic hepatitis C virus infection. J. Infect. Dis. 2004, 190:1919-1926.
62. Kawai T., Akira S. Innate immune recognition of viral infection. Nat. Immunol. 2006, 7:131-137.
63. Kawai T., Akira S. The role of pattern-recognition receptors in innate immunity: Update on Toll-like receptors. Nat. Immunol. 2010, 11:373-384.
64. Kim Y.M., Brinkmann M.M., Paquet M.E., Ploegh H.L. UNC93B1 delivers nucleotide-sensing toll-like receptors to endolysosomes. Nature 2008, 452:234-238.
65. Koyama S., Ishii K.J., Kumar H., Tanimoto T., Coban C., Uematsu S., Kawai T., Akira S. Differential role of TLR- and RLR-signaling in the immune responses to influenza A virus infection and vaccination. J. Immunol. 2007, 179:4711-4720.
66. Koyama S., Aoshi T., Tanimoto T., Kumagai Y., Kobiyama K., Tougan T., Sakurai K., Coban C., Horii T., Akira S., Ishii K.J. Plasmacytoid dendritic cells delineate immunogenicity of influenza vaccine subtypes. Sci. Transl. Med. 2010, 2:ra24.
67. Kropf P., Freudenberg M.A., Modolell M., Price H.P., Herath S., Antoniazi S., Galanos C., Smith D.F., Müller I. Toll-like receptor 4 contributes to efficient control of infection with the protozoan parasite Leishmania major. Infect. Immun. 2004, 72:1920-1928.
68. Kumagai Y., Takeuchi O., Kato H., Kumar H., Matsui K., Morii E., Aozasa K., Kawai T., Akira S. Alveolar macrophages are the primary interferon-alpha producer in pulmonary infection with RNA viruses. Immunity 2007, 27:240-252.
69. Kumar H., Koyama S., Ishii K.J., Kawai T., Akira S. Cutting edge: Cooperation of IPS-1- and TRIF-dependent pathways in poly IC-enhanced antibody production and cytotoxic T cell responses. J. Immunol. 2008, 180:683-687.
70. Kumar H., Kumagai Y., Tsuchida T., Koenig P.A., Satoh T., Guo Z., Jang M.H., Saitoh T., Akira S., Kawai T. Involvement of the NLRP3 inflammasome in innate and humoral adaptive immune responses to fungal beta-glucan. J. Immunol. 2009, 183:8061-8067.
71. Lamkanfi M., Malireddi R.K., Kanneganti T.D. Fungal zymosan and mannan activate the cryopyrin inflammasome. J. Biol. Chem. 2009, 284:20574-20581.
72. Le Goffic R., Balloy V., Lagranderie M., Alexopoulou L., Escriou N., Flavell R., Chignard M., Si-Tahar M. Detrimental contribution of the Toll-like receptor (TLR)3 to influenza A virus-induced acute pneumonia. PLoS Pathog. 2006, 2:e53.
73. Lee H.K., Lund J.M., Ramanathan B., Mizushima N., Iwasaki A. Autophagy-dependent viral recognition by plasmacytoid dendritic cells. Science 2007, 315:1398-1401.
74. Lemon S.M. Induction and evasion of innate antiviral responses by hepatitis C virus. J. Biol. Chem. 2010, 285:22741-22747.
75. Letran S.E., Lee S.J., Atif S.M., Uematsu S., Akira S., McSorley S.J. TLR5 functions as an endocytic receptor to enhance flagellin-specific adaptive immunity. Eur. J. Immunol. 2011, 41:29-38.
76. Longhi M.P., Trumpfheller C., Idoyaga J., Caskey M., Matos I., Kluger C., Salazar A.M., Colonna M., Steinman R.M. Dendritic cells require a systemic type I interferon response to mature and induce CD4+ Th1 immunity with poly IC as adjuvant. J. Exp. Med. 2009, 206:1589-1602.
77. Loo Y.-M., Gale M. Immune signaling by RIG-I-like receptors. Immunity 2011, 34:680-692. this issue.
78. Mancuso G., Gambuzza M., Midiri A., Biondo C., Papasergi S., Akira S., Teti G., Beninati C. Bacterial recognition by TLR7 in the lysosomes of conventional dendritic cells. Nat. Immunol. 2009, 10:587-594.
79. Marakalala M.J., Graham L.M., Brown G.D. The role of Syk/CARD9-coupled C-type lectin receptors in immunity to Mycobacterium tuberculosis infections. Clin. Dev. Immunol. 2010, 2010:567571.
80. Mayer-Barber K.D., Barber D.L., Shenderov K., White S.D., Wilson M.S., Cheever A., Kugler D., Hieny S., Caspar P., Núñez G., et al. Caspase-1 independent IL-1beta production is critical for host resistance to Mycobacterium tuberculosis and does not require TLR signaling in vivo. J. Immunol. 2010, 184:3326-3330.
81. McElvania Tekippe E., Allen I.C., Hulseberg P.D., Sullivan J.T., McCann J.R., Sandor M., Braunstein M., Ting J.P. Granuloma formation and host defense in chronic Mycobacterium tuberculosis infection requires PYCARD/ASC but not NLRP3 or caspase-1. PLoS ONE 2010, 5:e12320.
82. Medzhitov R. Recognition of microorganisms and activation of the immune response. Nature 2007, 449:819-826.
83. Melo M.B., Kasperkovitz P., Cerny A., Könen-Waisman S., Kurt-Jones E.A., Lien E., Beutler B., Howard J.C., Golenbock D.T., Gazzinelli R.T. UNC93B1 mediates host resistance to infection with Toxoplasma gondii. PLoS Pathog. 2010, 6:e1001071.
84. Miao E.A., Andersen-Nissen E., Warren S.E., Aderem A. TLR5 and Ipaf: Dual sensors of bacterial flagellin in the innate immune system. Semin. Immunopathol. 2007, 29:275-288.
85. Miller L.S., O'Connell R.M., Gutierrez M.A., Pietras E.M., Shahangian A., Gross C.E., Thirumala A., Cheung A.L., Cheng G., Modlin R.L. MyD88 mediates neutrophil recruitment initiated by IL-1R but not TLR2 activation in immunity against Staphylococcus aureus. Immunity 2006, 24:79-91.
86. Mócsai A., Ruland J., Tybulewicz V.L. The SYK tyrosine kinase: A crucial player in diverse biological functions. Nat. Rev. Immunol. 2010, 10:387-402.
87. Mun H.S., Aosai F., Norose K., Chen M., Piao L.X., Takeuchi O., Akira S., Ishikura H., Yano A. TLR2 as an essential molecule for protective immunity against Toxoplasma gondii infection. Int. Immunol. 2003, 15:1081-1087.
88. Negishi H., Osawa T., Ogami K., Ouyang X., Sakaguchi S., Koshiba R., Yanai H., Seko Y., Shitara H., Bishop K., et al. A critical link between Toll-like receptor 3 and type II interferon signaling pathways in antiviral innate immunity. Proc. Natl. Acad. Sci. USA 2008, 105:20446-20451.
89. Netea M.G., Maródi L. Innate immune mechanisms for recognition and uptake of Candida species. Trends Immunol. 2010, 31:346-353.
90. Netea M.G., Sutmuller R., Hermann C., Van der Graaf C.A., Van der Meer J.W., van Krieken J.H., Hartung T., Adema G., Kullberg B.J. Toll-like receptor 2 suppresses immunity against Candida albicans through induction of IL-10 and regulatory T cells. J. Immunol. 2004, 172:3712-3718.
91. Osorio F., Reis e Sousa C. Myeloid C-type lectin receptors in pathogen recogniztion and host defense. Immunity 2011, 34:651-664. this issue.
92. Palsson-McDermott E.M., Doyle S.L., McGettrick A.F., Hardy M., Husebye H., Banahan K., Gong M., Golenbock D., Espevik T., O'Neill L.A. TAG, a splice variant of the adaptor TRAM, negatively regulates the adaptor MyD88-independent TLR4 pathway. Nat. Immunol. 2009, 10:579-586.
93. Park B., Buti L., Lee S., Matsuwaki T., Spooner E., Brinkmann M.M., Nishihara M., Ploegh H.L. Granulin is a soluble cofactor for Toll-like Receptor 9 signaling. Immunity 2011, 34:505-513.
94. Pérez de Diego R., Sancho-Shimizu V., Lorenzo L., Puel A., Plancoulaine S., Picard C., Herman M., Cardon A., Durandy A., Bustamante J., et al. Human TRAF3 adaptor molecule deficiency leads to impaired Toll-like receptor 3 response and susceptibility to herpes simplex encephalitis. Immunity 2010, 33:400-411.
95. Picard C., Puel A., Bonnet M., Ku C.L., Bustamante J., Yang K., Soudais C., Dupuis S., Feinberg J., Fieschi C., et al. Pyogenic bacterial infections in humans with IRAK-4 deficiency. Science 2003, 299:2076-2079.
96. Pifer R., Benson A., Sturge C.R., Yarovinsky F. UNC93B1 is essential for TLR11 activation and IL-12-dependent host resistance to Toxoplasma gondii. J. Biol. Chem. 2011, 286:3307-3314.
97. Poeck H., Bscheider M., Gross O., Finger K., Roth S., Rebsamen M., Hannesschläger N., Schlee M., Rothenfusser S., Barchet W., et al. Recognition of RNA virus by RIG-I results in activation of CARD9 and inflammasome signaling for interleukin 1 beta production. Nat. Immunol. 2010, 11:63-69.
98. Rathinam V.A., Jiang Z., Waggoner S.N., Sharma S., Cole L.E., Waggoner L., Vanaja S.K., Monks B.G., Ganesan S., Latz E., et al. The AIM2 inflammasome is essential for host defense against cytosolic bacteria and DNA viruses. Nat. Immunol. 2010, 11:395-402.
99. Rehermann B. Hepatitis C virus versus innate and adaptive immune responses: A tale of coevolution and coexistence. J. Clin. Invest. 2009, 119:1745-1754.
100. Reizis B., Bunin A., Ghosh H.S., Lewis K.L., Sisirak V. Plasmacytoid dendritic cells: recent progress and open questions. Annu. Rev. Immunol. 2011, 29:163-183.
101. Romani L. Immunity to fungal infections. Nat. Rev. Immunol. 2011, 11:275-288.
102. Ropert C., Gazzinelli R.T. Regulatory role of Toll-like receptor 2 during infection with Trypanosoma cruzi. J. Endotoxin Res. 2004, 10:425-430.
103. Saiga H., Shimada Y., Takeda K. Innate immune effectors in mycobacterial infection. Clin. Dev. Immunol. 2011, 2011:347594.
104. Saitoh S., Miyake K. Regulatory molecules required for nucleotide-sensing Toll-like receptors. Immunol. Rev. 2009, 227:32-43.
105. Saitoh T., Satoh T., Yamamoto N., Uematsu S., Takeuchi O., Kawai T., Akira S. Antiviral protein Viperin promotes Toll-like receptor 7- and Toll-like receptor 9-mediated type I interferon production in plasmacytoid dendritic cells. Immunity 2011, 34:352-363.
106. Sasai M., Linehan M.M., Iwasaki A. Bifurcation of Toll-like receptor 9 signaling by adaptor protein 3. Science 2010, 329:1530-1534.
107. Schoenen H., Bodendorfer B., Hitchens K., Manzanero S., Werninghaus K., Nimmerjahn F., Agger E.M., Stenger S., Andersen P., Ruland J., et al. Cutting edge: Mincle is essential for recognition and adjuvanticity of the mycobacterial cord factor and its synthetic analog trehalose-dibehenate. J. Immunol. 2010, 184:2756-2760.
108. Schulz O., Diebold S.S., Chen M., Näslund T.I., Nolte M.A., Alexopoulou L., Azuma Y.T., Flavell R.A., Liljeström P., Reis e Sousa C. Toll-like receptor 3 promotes cross-priming to virus-infected cells. Nature 2005, 433:887-892.
109. Seo S.U., Kwon H.J., Song J.H., Byun Y.H., Seong B.L., Kawai T., Akira S., Kweon M.N. MyD88 signaling is indispensable for primary influenza A virus infection but dispensable for secondary infection. J. Virol. 2010, 84:12713-12722.
110. Shi Z., Cai Z., Sanchez A., Zhang T., Wen S., Wang J., Yang J., Fu S., Zhang D. A novel Toll-like receptor that recognizes vesicular stomatitis virus. J. Biol. Chem. 2011, 286:4517-4524.
111. Shiina M., Rehermann B. Cell culture-produced hepatitis C virus impairs plasmacytoid dendritic cell function. Hepatology 2008, 47:385-395.
112. Shio M.T., Eisenbarth S.C., Savaria M., Vinet A.F., Bellemare M.J., Harder K.W., Sutterwala F.S., Bohle D.S., Descoteaux A., Flavell R.A., Olivier M. Malarial hemozoin activates the NLRP3 inflammasome through Lyn and Syk kinases. PLoS Pathog. 2009, 5:e1000559.
113. Spreafico R., Ricciardi-Castagnoli P., Mortellaro A. The controversial relationship between NLRP3, alum, danger signals and the next-generation adjuvants. Eur. J. Immunol. 2010, 40:638-642.
114. Sutmuller R.P., den Brok M.H., Kramer M., Bennink E.J., Toonen L.W., Kullberg B.J., Joosten L.A., Akira S., Netea M.G., Adema G.J. Toll-like receptor 2 controls expansion and function of regulatory T cells. J. Clin. Invest. 2006, 116:485-494.
115. Tabeta K., Georgel P., Janssen E., Du X., Hoebe K., Crozat K., Mudd S., Shamel L., Sovath S., Goode J., et al. Toll-like receptors 9 and 3 as essential components of innate immune defense against mouse cytomegalovirus infection. Proc. Natl. Acad. Sci. USA 2004, 101:3516-3521.
116. Tabeta K., Hoebe K., Janssen E.M., Du X., Georgel P., Crozat K., Mudd S., Mann N., Sovath S., Goode J., et al. The Unc93b1 mutation 3d disrupts exogenous antigen presentation and signaling via Toll-like receptors 3, 7 and 9. Nat. Immunol. 2006, 7:156-164.
117. Takahashi K., Asabe S., Wieland S., Garaigorta U., Gastaminza P., Isogawa M., Chisari F.V. Plasmacytoid dendritic cells sense hepatitis C virus-infected cells, produce interferon, and inhibit infection. Proc. Natl. Acad. Sci. USA 2010, 107:7431-7436.
118. Takeuchi O., Hoshino K., Akira S. Cutting edge: TLR2-deficient and MyD88-deficient mice are highly susceptible to Staphylococcus aureus infection. J. Immunol. 2000, 165:5392-5396.
119. Uematsu S., Jang M.H., Chevrier N., Guo Z., Kumagai Y., Yamamoto M., Kato H., Sougawa N., Matsui H., Kuwata H., et al. Detection of pathogenic intestinal bacteria by Toll-like receptor 5 on intestinal CD11c+ lamina propria cells. Nat. Immunol. 2006, 7:868-874.
120. Uematsu S., Fujimoto K., Jang M.H., Yang B.G., Jung Y.J., Nishiyama M., Sato S., Tsujimura T., Yamamoto M., Yokota Y., et al. Regulation of humoral and cellular gut immunity by lamina propria dendritic cells expressing Toll-like receptor 5. Nat. Immunol. 2008, 9:769-776.
121. Verdrengh M., Thomas J.A., Hultgren O.H. IL-1 receptor-associated kinase 1 mediates protection against Staphylococcus aureus infection. Microbes Infect. 2004, 6:1268-1272.
122. Vijay-Kumar M., Carvalho F.A., Aitken J.D., Fifadara N.H., Gewirtz A.T. TLR5 or NLRC4 is necessary and sufficient for promotion of humoral immunity by flagellin. Eur. J. Immunol. 2010, 40:3528-3534.
123. Villadangos J.A., Shortman K. Found in translation: The human equivalent of mouse CD8+ dendritic cells. J. Exp. Med. 2010, 207:1131-1134.
124. von Bernuth H., Picard C., Jin Z., Pankla R., Xiao H., Ku C.L., Chrabieh M., Mustapha I.B., Ghandil P., Camcioglu Y., et al. Pyogenic bacterial infections in humans with MyD88 deficiency. Science 2008, 321:691-696.
125. Wang T., Town T., Alexopoulou L., Anderson J.F., Fikrig E., Flavell R.A. Toll-like receptor 3 mediates West Nile virus entry into the brain causing lethal encephalitis. Nat. Med. 2004, 10:1366-1373.
126. Weiss D.S., Raupach B., Takeda K., Akira S., Zychlinsky A. Toll-like receptors are temporally involved in host defense. J. Immunol. 2004, 172:4463-4469.
127. Werninghaus K., Babiak A., Gross O., Hölscher C., Dietrich H., Agger E.M., Mages J., Mocsai A., Schoenen H., Finger 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. 2009, 206:89-97.
128. West A.P., Brodsky I.E., Rahner C., Woo D.K., Erdjument-Bromage H., Tempst P., Walsh M.C., Choi Y., Shadel G.S., Ghosh S. TLR signalling augments macrophage bactericidal activity through mitochondrial ROS. Nature 2011, 472:476-480.
129. Yanai H., Ban T., Wang Z., Choi M.K., Kawamura T., Negishi H., Nakasato M., Lu Y., Hangai S., Koshiba R., et al. HMGB proteins function as universal sentinels for nucleic-acid-mediated innate immune responses. Nature 2009, 462:99-103.
130. Yarovinsky F., Zhang D., Andersen J.F., Bannenberg G.L., Serhan C.N., Hayden M.S., Hieny S., Sutterwala F.S., Flavell R.A., Ghosh S., Sher A. TLR11 activation of dendritic cells by a protozoan profilin-like protein. Science 2005, 308:1626-1629.
131. Zhang S.Y., Jouanguy E., Ugolini S., Smahi A., Elain G., Romero P., Segal D., Sancho-Shimizu V., Lorenzo L., Puel A., et al. TLR3 deficiency in patients with herpes simplex encephalitis. Science 2007, 317:1522-1527.