dsRNA sensors and plasmacytoid dendritic cells in host defense and autoimmunity

Immunological Reviews

Volumn 243, Issue 1, 2011, Pages 74-90

  Wang, Yaming ^a   Swiecki, Melissa ^a   McCartney, Stephen A ^a   Colonna, Marco ^a  

^a WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Autoimmunity; Dendritic cells; Diabetes; Systemic lupus erythematosus; Toll like receptors pattern recognition receptors; Virus

Indexed keywords

BETA1A INTERFERON; DOUBLE STRANDED RNA; IMIQUIMOD; INTERFERON; PATTERN RECOGNITION RECEPTOR; POLYINOSINIC POLYCYTIDYLIC ACID; RETINOIC ACID INDUCIBLE PROTEIN I; RIBONUCLEASE L; SINGLE STRANDED RNA; TOLL LIKE RECEPTOR 7; TOLL LIKE RECEPTOR 9; VIRUS DNA; VIRUS RNA;

ALLERGIC ENCEPHALOMYELITIS; ANTIGEN PRESENTING CELL; APOPTOSIS; AUTOIMMUNE DISEASE; AUTOIMMUNITY; CELL ACTIVATION; CELL INFILTRATION; CELL SURVIVAL; CELL TYPE; CYTOKINE RELEASE; DENDRITIC CELL; DISEASE EXACERBATION; DOUBLE STRANDED RNA SENSOR; ENCEPHALOMYOCARDITIS VIRUS; ENDOPLASMIC RETICULUM; ENZYME PHOSPHORYLATION; GENE MUTATION; GENE REGULATORY NETWORK; GENETIC VARIABILITY; GENOME; GENOME SIZE; GENOME STRUCTURE; GENOMIC COMPOSITION; HERPES SIMPLEX; HERPES SIMPLEX VIRUS 1; HOST RESISTANCE; HUMAN; HYPERGLYCEMIA; IMMUNE RESPONSE; IMMUNE SYSTEM; IMMUNOLOGICAL TOLERANCE; IMMUNOPATHOGENESIS; IMMUNOTHERAPY; INNATE IMMUNITY; INSULIN DEPENDENT DIABETES MELLITUS; INSULITIS; INTERFERON PRODUCTION; LIGAND BINDING; LUPUS LIKE SYNDROME; MOLECULAR SENSOR; MOLLUSCUM CONTAGIOSUM; MULTIPLE SCLEROSIS; NATURAL KILLER CELL; NONHUMAN; PANCREAS ISLET BETA CELL; PLASMACYTOID DENDRITIC CELL; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; PSORIASIS; REVIEW; RNA REPLICATION; RNA TRANSLATION; SIGNAL TRANSDUCTION; SKIN CANCER; SKIN PAPILLOMA; SYSTEMIC LUPUS ERYTHEMATOSUS; TROPISM; VIRUS DETECTION; VIRUS IMMUNITY; VIRUS INFECTION; VIRUS REPLICATION; WEST NILE FLAVIVIRUS;

ANIMALS; ANTIGENIC VARIATION; AUTOIMMUNITY; DENDRITIC CELLS; HOST-PATHOGEN INTERACTIONS; HUMANS; IMMUNITY, INNATE; INFLAMMATION MEDIATORS; INTERFERON TYPE I; RECEPTOR CROSS-TALK; RNA, DOUBLE-STRANDED; SIGNAL TRANSDUCTION; VIRAL TROPISM; VIRUS DISEASES; VIRUSES;

EID: 80052180597     PISSN: 01052896     EISSN: 1600065X     Source Type: Journal    
DOI: 10.1111/j.1600-065X.2011.01049.x     Document Type: Review

References (258)

1. Pestka S, Krause CD, Walter MR. Interferons, interferon-like cytokines, and their receptors. Immunol Rev 2004;202:8-32.
2. Malathi K, et al. A transcriptional signaling pathway in the IFN system mediated by 2'-5'-oligoadenylate activation of RNase L. Proc Natl Acad Sci USA 2005;102:14533-14538.
3. Malathi K, Dong B, Gale M Jr, Silverman RH. Small self-RNA generated by RNase L amplifies antiviral innate immunity. Nature 2007;448:816-819.
4. Barber GN, Wambach M, Wong ML, Dever TE, Hinnebusch AG, Katze MG. Translational regulation by the interferon-induced double-stranded-RNA-activated 68-kDa protein kinase. Proc Natl Acad Sci USA 1993;90:4621-4625.
5. Theofilopoulos AN, Baccala R, Beutler B, Kono DH. Type I interferons (alpha/beta) in immunity and autoimmunity. Annu Rev Immunol 2005;23:307-336.
6. Trinchieri G. Type I interferon: friend or foe? J Exp Med 2010;207:2053-2063.
7. Stetson DB, Medzhitov R. Type I interferons in host defense. Immunity 2006;25:373-381.
8. Takeuchi O, Akira S. Recognition of viruses by innate immunity. Immunol Rev 2007;220:214-224.
9. Lemaitre B, Nicolas E, Michaut L, Reichhart JM, Hoffmann JA. The dorsoventral regulatory gene cassette spatzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell 1996;86:973-983.
10. Pichlmair A, Reis e Sousa C. Innate recognition of viruses. Immunity 2007;27:370-383.
11. Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol 2010;11:373-384.
12. Boehme KW, Guerrero M, Compton T. Human cytomegalovirus envelope glycoproteins B and H are necessary for TLR2 activation in permissive cells. J Immunol 2006;177:7094-7102.
13. Compton T, et al. Human cytomegalovirus activates inflammatory cytokine responses via CD14 and Toll-like receptor 2. J Virol 2003;77:4588-4596.
14. Sato A, Linehan MM, Iwasaki A. Dual recognition of herpes simplex viruses by TLR2 and TLR9 in dendritic cells. Proc Natl Acad Sci USA 2006;103:17343-17348.
15. Kurt-Jones EA, et al. Herpes simplex virus 1 interaction with Toll-like receptor 2 contributes to lethal encephalitis. Proc Natl Acad Sci USA 2004;101:1315-1320.
16. Chang S, Dolganiuc A, Szabo G. Toll-like receptors 1 and 6 are involved in TLR2-mediated macrophage activation by hepatitis C virus core and NS3 proteins. J Leuk Biol 2007;82:479-487.
17. Bieback K, et al. Hemagglutinin protein of wild-type measles virus activates toll-like receptor 2 signaling. J Virol 2002;76:8729-8736.
18. Zhu J, Martinez J, Huang X, Yang Y. Innate immunity against vaccinia virus is mediated by TLR2 and requires TLR-independent production of IFN-beta. Blood 2007;109:619-625.
19. Zhou S, et al. MyD88 is critical for the development of innate and adaptive immunity during acute lymphocytic choriomeningitis virus infection. Eur J Immunol 2005;35:822-830.
20. Barbalat R, Lau L, Locksley RM, Barton GM. 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.
21. Thompson JM, Iwasaki A. Toll-like receptors regulation of viral infection and disease. Adv Drug Deliv Rev 2008;60:786-794.
22. Blasius AL, Beutler B. Intracellular toll-like receptors. Immunity 2010;32:305-315.
23. Tabeta K, 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.
24. Brinkmann MM, Spooner E, Hoebe K, Beutler B, Ploegh HL, Kim YM. 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.
25. Alexopoulou L, Holt AC, Medzhitov R, Flavell RA. Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature 2001;413:732-738.
26. Schulz O, et al. Toll-like receptor 3 promotes cross-priming to virus-infected cells. Nature 2005;433:887-892.
27. + dendritic cell subset. Immunol Rev 2010;234:18-31.
28. Yamamoto M, et al. Cutting edge: a novel Toll/IL-1 receptor domain-containing adapter that preferentially activates the IFN-beta promoter in the Toll-like receptor signaling. J Immunol 2002;169:6668-6672.
29. Oshiumi H, Matsumoto M, Funami K, Akazawa T, Seya T. TICAM-1, an adaptor molecule that participates in Toll-like receptor 3-mediated interferon-beta induction. Nat Immunol 2003;4:161-167.
30. Sato S, et al. Toll/IL-1 receptor domain-containing adaptor inducing IFN-beta (TRIF) associates with TNF receptor-associated factor 6 and TANK-binding kinase 1, and activates two distinct transcription factors, NF-kappa B and IFN-regulatory factor-3, in the Toll-like receptor signaling. J Immunol 2003;171:4304-4310.
31. Oganesyan G, et al. Critical role of TRAF3 in the Toll-like receptor-dependent and -independent antiviral response. Nature 2006;439:208-211.
32. Hacker H, et al. Specificity in Toll-like receptor signalling through distinct effector functions of TRAF3 and TRAF6. Nature 2006;439:204-207.
33. Jacquemont B, Roizman B. RNA synthesis in cells infected with herpes simplex virus. X. Properties of viral symmetric transcripts and of double-stranded RNA prepared from them. J Virol 1975;15:707-713.
34. Casrouge A, et al. Herpes simplex virus encephalitis in human UNC-93B deficiency. Science 2006;314:308-312.
35. Zhang SY, et al. TLR3 deficiency in patients with herpes simplex encephalitis. Science 2007;317:1522-1527.
36. Perez de Diego R, 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.
37. Sancho-Shimizu V, et al. Genetic susceptibility to herpes simplex virus 1 encephalitis in mice and humans. Curr Opin Allergy Clin Immunol 2007;7:495-505.
38. Davey GM, Wojtasiak M, Proietto AI, Carbone FR, Heath WR, Bedoui S. Cutting edge: priming of CD8 T cell immunity to herpes simplex virus type 1 requires cognate TLR3 expression in vivo. J Immunol 2010;184:2243-2246.
39. Gowen BB, et al. TLR3 deletion limits mortality and disease severity due to Phlebovirus infection. J Immunol 2006;177:6301-6307.
40. Le Goffic R, et al. Detrimental contribution of the Toll-like receptor (TLR)3 to influenza A virus-induced acute pneumonia. PLoS Pathog 2006;2:e53.
41. Heil F, et al. Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8. Science 2004;303:1526-1529.
42. Diebold SS, Kaisho T, Hemmi H, Akira S, Reis e Sousa C. Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA. Science 2004;303:1529-1531.
43. Lund JM, et al. Recognition of single-stranded RNA viruses by Toll-like receptor 7. Proc Natl Acad Sci USA 2004;101:5598-5603.
44. Bauer S, et al. Human TLR9 confers responsiveness to bacterial DNA via species-specific CpG motif recognition. Proc Natl Acad Sci USA 2001;98:9237-9242.
45. Martinez J, Huang X, Yang Y. Toll-like receptor 8-mediated activation of murine plasmacytoid dendritic cells by vaccinia viral DNA. Proc Natl Acad Sci USA 2010;107: 6442-6447.
46. Iwasaki A, Medzhitov R. Toll-like receptor control of the adaptive immune responses. Nat Immunol 2004;5:987-995.
47. Gilliet M, Cao W, Liu YJ. Plasmacytoid dendritic cells: sensing nucleic acids in viral infection and autoimmune diseases. Nat Rev Immunol 2008;8:594-606.
48. Shinohara ML, et al. Osteopontin expression is essential for interferon-alpha production by plasmacytoid dendritic cells. Nat Immunol 2006;7:498-506.
49. Honda K, et al. IRF-7 is the master regulator of type-I interferon-dependent immune responses. Nature 2005;434:772-777.
50. Honda K, Takaoka A, Taniguchi T. Type I interferon gene induction by the interferon regulatory factor family of transcription factors. Immunity 2006;25:349-360.
51. Cao W, et al. Toll-like receptor-mediated induction of type I interferon in plasmacytoid dendritic cells requires the rapamycin-sensitive PI(3)K-mTOR-p70S6K pathway. Nat Immunol 2008;9:1157-1164.
52. Colina R, et al. Translational control of the innate immune response through IRF-7. Nature 2008;452:323-328.
53. Takaoka A, et al. Integral role of IRF-5 in the gene induction programme activated by Toll-like receptors. Nature 2005;434:243-249.
54. Guiducci C, et al. Properties regulating the nature of the plasmacytoid dendritic cell response to Toll-like receptor 9 activation. J Exp Med 2006;203:1999-2008.
55. Cao W, Liu YJ. Innate immune functions of plasmacytoid dendritic cells. Curr Opin Immunol 2007;19:24-30.
56. Sasai M, Linehan MM, Iwasaki A. Bifurcation of Toll-like receptor 9 signaling by adaptor protein 3. Science 2010;329:1530-1534.
57. Blasius AL, et al. Slc15a4, AP-3, and Hermansky-Pudlak syndrome proteins are required for Toll-like receptor signaling in plasmacytoid dendritic cells. Proc Natl Acad Sci USA 2010;107:19973-19978.
58. Park B, Brinkmann MM, Spooner E, Lee CC, Kim YM, Ploegh HL. Proteolytic cleavage in an endolysosomal compartment is required for activation of Toll-like receptor 9. Nat Immunol 2008;9:1407-1414.
59. Ewald SE, et al. The ectodomain of Toll-like receptor 9 is cleaved to generate a functional receptor. Nature 2008;456:658-662.
60. Ewald SE, Engel A, Lee J, Wang M, Bogyo M, Barton GM. Nucleic acid recognition by Toll-like receptors is coupled to stepwise processing by cathepsins and asparagine endopeptidase. J Exp Med 2011;208:643-651.
61. Park B, et al. Granulin is a soluble cofactor for Toll-like receptor 9 signaling. Immunity 2011;34:505-513.
62. Mancuso G, et al. Bacterial recognition by TLR7 in the lysosomes of conventional dendritic cells. Nat Immunol 2009;10:587-594.
63. Hoshino K, et al. Critical role of IkappaB Kinase alpha in TLR7/9-induced type I IFN production by conventional dendritic cells. J Immunol 2010;184:3341-3345.
64. Yoneyama M, Fujita T. RNA recognition and signal transduction by RIG-I-like receptors. Immunol Rev 2009;227:54-65.
65. Yoneyama M, et al. The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses. Nat Immunol 2004;5:730-737.
66. Kang DC, Gopalkrishnan RV, Wu Q, Jankowsky E, Pyle AM, Fisher PB. mda-5: an interferon-inducible putative RNA helicase with double-stranded RNA-dependent ATPase activity and melanoma growth-suppressive properties. Proc Natl Acad Sci USA 2002;99:637-642.
67. Kovacsovics M, Martinon F, Micheau O, Bodmer JL, Hofmann K, Tschopp J. Overexpression of Helicard, a CARD-containing helicase cleaved during apoptosis, accelerates DNA degradation. Curr Biol 2002;12:838-843.
68. Saito T, et al. Regulation of innate antiviral defenses through a shared repressor domain in RIG-I and LGP2. Proc Natl Acad Sci USA 2007;104:582-587.
69. Kato H, et al. Length-dependent recognition of double-stranded ribonucleic acids by retinoic acid-inducible gene-I and melanoma differentiation-associated gene 5. J Exp Med 2008;205:1601-1610.
70. Saito T, Gale M Jr. Differential recognition of double-stranded RNA by RIG-I-like receptors in antiviral immunity. J Exp Med 2008;205:1523-1527.
71. Kato H, et al. Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. Nature 2006;441:101-105.
72. Gitlin L, et al. Essential role of mda-5 in type I IFN responses to polyriboinosinic:polyribocytidylic acid and encephalomyocarditis picornavirus. Proc Natl Acad Sci USA 2006;103:8459-8464.
73. Zust R, et al. Ribose 2'-O-methylation provides a molecular signature for the distinction of self and non-self mRNA dependent on the RNA sensor Mda5. Nat Immunol 2011;12:137-143.
74. Loo YM, et al. Viral and therapeutic control of IFN-beta promoter stimulator 1 during hepatitis C virus infection. Proc Natl Acad Sci USA 2006;103:6001-6006.
75. Gitlin L, et al. Melanoma differentiation-associated gene 5 (MDA5) is involved in the innate immune response to Paramyxoviridae infection in vivo. PLoS Pathog 2010;6:e1000734.
76. Furr SR, Chauhan VS, Sterka D Jr, Grdzelishvili V, Marriott I. Characterization of retinoic acid-inducible gene-I expression in primary murine glia following exposure to vesicular stomatitis virus. J Neurovirol 2008;14:503-513.
77. Chiu YH, Macmillan JB, Chen ZJ. RNA polymerase III detects cytosolic DNA and induces type I interferons through the RIG-I pathway. Cell 2009;138:576-591.
78. Ablasser A, Bauernfeind F, Hartmann G, Latz E, Fitzgerald KA, Hornung V. RIG-I-dependent sensing of poly(dA:dT) through the induction of an RNA polymerase III-transcribed RNA intermediate. Nat Immunol 2009;10:1065-1072.
79. Kawai T, et al. IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction. Nat Immunol 2005;6:981-988.
80. Seth RB, Sun L, Ea CK, Chen ZJ. Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF 3. Cell 2005;122:669-682.
81. Kumar H, et al. Essential role of IPS-1 in innate immune responses against RNA viruses. J Exp Med 2006;203:1795-1803.
82. Xu LG, Wang YY, Han KJ, Li LY, Zhai Z, Shu HB. VISA is an adapter protein required for virus-triggered IFN-beta signaling. Mol Cell 2005;19:727-740.
83. Saha SK, et al. Regulation of antiviral responses by a direct and specific interaction between TRAF3 and Cardif. EMBO J 2006;25:3257-3263.
84. Sharma S, tenOever BR, Grandvaux N, Zhou GP, Lin R, Hiscott J. Triggering the interferon antiviral response through an IKK-related pathway. Science 2003;300:1148-1151.
85. Fitzgerald KA, et al. IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway. Nat Immunol 2003;4:491-496.
86. Balachandran S, Thomas E, Barber GN. A FADD-dependent innate immune mechanism in mammalian cells. Nature 2004;432:401-405.
87. Takahashi K, Kawai T, Kumar H, Sato S, Yonehara S, Akira S. Roles of caspase-8 and caspase-10 in innate immune responses to double-stranded RNA. J Immunol 2006;176:4520-4524.
88. Rothenfusser S, et al. The RNA helicase Lgp2 inhibits TLR-independent sensing of viral replication by retinoic acid-inducible gene-I. J Immunol 2005;175:5260-5268.
89. Venkataraman T, et al. Loss of DExD/H box RNA helicase LGP2 manifests disparate antiviral responses. J Immunol 2007;178:6444-6455.
90. Satoh T, et al. LGP2 is a positive regulator of RIG-I- and MDA5-mediated antiviral responses. Proc Natl Acad Sci USA 2010;107:1512-1517.
91. Gack MU, et al. TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated antiviral activity. Nature 2007; 446:916-920.
92. Wang P, et al. Caspase-12 controls West Nile virus infection via the viral RNA receptor RIG-I. Nat Immunol 2010;11:912-919.
93. Rajput A, et al. RIG-I RNA helicase activation of IRF3 transcription factor is negatively regulated by caspase-8-mediated cleavage of the RIP1 protein. Immunity 2011;34:340-351.
94. Hou J, et al. MicroRNA-146a feedback inhibits RIG-I-dependent Type I IFN production in macrophages by targeting TRAF6, IRAK1, and IRAK2. J Immunol 2009;183:2150-2158.
95. Cardenas WB, et al. Ebola virus VP35 protein binds double-stranded RNA and inhibits alpha/beta interferon production induced by RIG-I signaling. J Virol 2006;80:5168-5178.
96. Andrejeva J, et al. The V proteins of paramyxoviruses bind the IFN-inducible RNA helicase, mda-5, and inhibit its activation of the IFN-beta promoter. Proc Natl Acad Sci USA 2004;101:17264-17269.
97. Barber GN. Innate immune DNA sensing pathways: STING, AIMII and the regulation of interferon production and inflammatory responses. Curr Opin Immunol 2011;23:10-20.
98. Takeuchi O, Akira S. Pattern recognition receptors and inflammation. Cell 2010;140:805-820.
99. Takaoka A, et al. DAI (DLM-1/ZBP1) is a cytosolic DNA sensor and an activator of innate immune response. Nature 2007;448:501-505.
100. Wang Z, et al. Regulation of innate immune responses by DAI (DLM-1/ZBP1) and other DNA-sensing molecules. Proc Natl Acad Sci USA 2008;105:5477-5482.
101. Ishii KJ, et al. TANK-binding kinase-1 delineates innate and adaptive immune responses to DNA vaccines. Nature 2008;451:725-729.
102. Lippmann J, et al. IFNbeta responses induced by intracellular bacteria or cytosolic DNA in different human cells do not require ZBP1 (DLM-1/DAI). Cell Microbiol 2008;10:2579-2588.
103. Unterholzner L, et al. IFI16 is an innate immune sensor for intracellular DNA. Nat Immunol 2010;11:997-1004.
104. Zhong B, et al. The adaptor protein MITA links virus-sensing receptors to IRF3 transcription factor activation. Immunity 2008;29:538-550.
105. Ishikawa H, Ma Z, Barber GN. STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity. Nature 2009;461:788-792.
106. Ishikawa H, Barber GN. STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling. Nature 2008;455:674-678.
107. Yanai H, et al. HMGB proteins function as universal sentinels for nucleic-acid-mediated innate immune responses. Nature 2009;462:99-103.
108. Kim T, et al. Aspartate-glutamate-alanine-histidine box motif (DEAH)/RNA helicase A helicases sense microbial DNA in human plasmacytoid dendritic cells. Proc Natl Acad Sci USA 2010;107:15181-15186.
109. Burckstummer T, et al. An orthogonal proteomic-genomic screen identifies AIM2 as a cytoplasmic DNA sensor for the inflammasome. Nat Immunol 2009;10:266-272.
110. Fernandes-Alnemri T, Yu JW, Datta P, Wu J, Alnemri ES. AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA. Nature 2009;458:509-513.
111. Roberts TL, et al. HIN-200 proteins regulate caspase activation in response to foreign cytoplasmic DNA. Science 2009;323:1057-1060.
112. Rathinam VA, et al. The AIM2 inflammasome is essential for host defense against cytosolic bacteria and DNA viruses. Nat Immunol 2010;11:395-402.
113. Allen IC, et al. The NLRP3 inflammasome mediates in vivo innate immunity to influenza A virus through recognition of viral RNA. Immunity 2009;30:556-565.
114. Ichinohe T, Lee HK, Ogura Y, Flavell R, Iwasaki A. Inflammasome recognition of influenza virus is essential for adaptive immune responses. J Exp Med 2009;206:79-87.
115. Kanneganti TD, et al. Critical role for Cryopyrin/Nalp3 in activation of caspase-1 in response to viral infection and double-stranded RNA. J Biol Chem 2006;281:36560-36568.
116. Kanneganti TD, et al. Bacterial RNA and small antiviral compounds activate caspase-1 through cryopyrin/Nalp3. Nature 2006;440:233-236.
117. Thomas PG, et al. The intracellular sensor NLRP3 mediates key innate and healing responses to influenza A virus via the regulation of caspase-1. Immunity 2009;30:566-575.
118. Muruve DA, et al. The inflammasome recognizes cytosolic microbial and host DNA and triggers an innate immune response. Nature 2008;452:103-107.
119. Kanneganti TD. Central roles of NLRs and inflammasomes in viral infection. Nat Rev Immunol 2010;10:688-698.
120. Schroder K, Tschopp J. The inflammasomes. Cell 2010;140:821-832.
121. Elinav E, Strowig T, Henao-Mejia J, Flavell RA. Regulation of the Antimicrobial Response by NLR Proteins. Immunity 2011;34:665-679.
122. Yoon JW, McClintock PR, Onodera T, Notkins AL. Virus-induced diabetes mellitus. XVIII. Inhibition by a nondiabetogenic variant of encephalomyocarditis virus. J Exp Med 1980;152:878-892.
123. Hardarson HS, et al. Toll-like receptor 3 is an essential component of the innate stress response in virus-induced cardiac injury. Am J Physiol Heart Circ Physiol 2007;292: H251-H258.
124. McCartney SA, et al. RNA sensor-induced type I IFN prevents diabetes caused by a beta cell-tropic virus in mice. J Clin Invest 2010;121:1497-1507.
125. Hober D, Sauter P. Pathogenesis of type 1 diabetes mellitus: interplay between enterovirus and host. Nat Rev Endocrinol 2010;6:279-289.
126. Richer MJ, Horwitz MS. Coxsackievirus infection as an environmental factor in the etiology of type 1 diabetes. Autoimmun Rev 2009;8:611-615.
127. Fujinami RS, von Herrath MG, Christen U, Whitton JL. Molecular mimicry, bystander activation, or viral persistence: infections and autoimmune disease. Clin Microbiol Rev 2006;19:80-94.
128. Richer MJ, Lavallee DJ, Shanina I, Horwitz MS. Toll-like receptor 3 signaling on macrophages is required for survival following coxsackievirus B4 infection. PLoS ONE 2009;4:e4127.
129. Huhn MH, McCartney SA, Lind K, Svedin E, Colonna M, Flodstrom-Tullberg M. Melanoma differentiation-associated protein-5 (MDA-5) limits early viral replication but is not essential for the induction of type 1 interferons after Coxsackievirus infection. Virology 2010;401:42-48.
130. Levine AS, Sivulich M, Wiernik PH, Levy HB. Initial clinical trials in cancer patients of polyriboinosinic-polyribocytidylic acid stabilized with poly-L-lysine, in carboxymethylcellulose [poly(ICLC)], a highly effective interferon inducer. Cancer Res 1979;39:1645-1650.
131. Levine AS, Levy HB. Phase I-II trials of poly IC stabilized with poly-L-lysine. Cancer Treat Rep 1978;62:1907-1912.
132. Robinson RA, DeVita VT, Levy HB, Baron S, Hubbard SP, Levine AS. A phase I-II trial of multiple-dose polyriboinosic-polyribocytidylic acid in patieonts with leukemia or solid tumors. J Natl Cancer Inst 1976;57:599-602.
133. McCartney S, et al. Distinct and complementary functions of MDA5 and TLR3 in poly(I:C)-mediated activation of mouse NK cells. J Exp Med 2009;206:2967-2976.
134. + T cell immunity together with a dendritic cell targeted vaccine. Proc Natl Acad Sci USA 2008;105:2574-2579.
135. Stahl-Hennig C, et al. Synthetic double-stranded RNAs are adjuvants for the induction of T helper 1 and humoral immune responses to human papillomavirus in rhesus macaques. PLoS Pathog 2009;5:e1000373.
136. + Th1 immunity with poly IC as adjuvant. J Exp Med 2009;206:1589-1602.
137. Kumar H, et al. 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.
138. Wang Y, Cella M, Gilfillan S, Colonna M. Cutting edge: polyinosinic:polycytidylic acid boosts the generation of memory CD8 T cells through melanoma differentiation associated protein 5 expressed in stromal cells. J Immunol 2010;184:2751-2755.
139. Thompson LJ, Kolumam GA, Thomas S, Murali-Krishna K. Innate inflammatory signals induced by various pathogens differentially dictate the IFN-I dependence of CD8 T cells for clonal expansion and memory formation. J Immunol 2006;177:1746-1754.
140. Kolumam GA, Thomas S, Thompson LJ, Sprent J, Murali-Krishna K. Type I interferons act directly on CD8 T cells to allow clonal expansion and memory formation in response to viral infection. J Exp Med 2005;202:637-650.
141. + T cell response during cross-priming. J Immunol 2006;176:4682-4689.
142. Sivori S, et al. CpG and double-stranded RNA trigger human NK cells by Toll-like receptors: induction of cytokine release and cytotoxicity against tumors and dendritic cells. Proc Natl Acad Sci USA 2004;101:10116-10121.
143. Schmidt KN, et al. APC-independent activation of NK cells by the Toll-like receptor 3 agonist double-stranded RNA. J Immunol 2004;172:138-143.
144. Lauzon NM, Mian F, MacKenzie R, Ashkar AA. The direct effects of Toll-like receptor ligands on human NK cell cytokine production and cytotoxicity. Cell Immunol 2006;241:102-112.
145. Hart OM, Athie-Morales V, O'Connor GM, Gardiner CM. TLR7/8-mediated activation of human NK cells results in accessory cell-dependent IFN-gamma production. J Immunol 2005;175:1636-1642.
146. Akazawa T, et al. Antitumor NK activation induced by the Toll-like receptor 3-TICAM-1 (TRIF) pathway in myeloid dendritic cells. Proc Natl Acad Sci USA 2007;104:252-257.
147. Miyake T, et al. Poly I:C-induced activation of NK cells by CD8 alpha+ dendritic cells via the IPS-1 and TRIF-dependent pathways. J Immunol 2009;183:2522-2528.
148. Allenspach EJ, Lemos MP, Porrett PM, Turka LA, Laufer TM. Migratory and lymphoid-resident dendritic cells cooperate to efficiently prime naive CD4 T cells. Immunity 2008;29:795-806.
149. Klein I, et al. Kupffer cell heterogeneity: functional properties of bone marrow derived and sessile hepatic macrophages. Blood 2007;110:4077-4085.
150. Siegal FP, et al. The nature of the principal type 1 interferon-producing cells in human blood. Science 1999;284:1835-1837.
151. Cella M, et al. Plasmacytoid monocytes migrate to inflamed lymph nodes and produce large amounts of type I interferon. Nat Med 1999;5:919-923.
152. Ronnblom L, Forsgren A, Alm GV. Characterization of interferons induced by bacteria and interferon-producing leukocytes in human peripheral blood. Infect Immun 1983;40:126-132.
153. Perussia B, Fanning V, Trinchieri G. A leukocyte subset bearing HLA-DR antigens is responsible for in vitro alpha interferon production in response to viruses. Nat Immun Cell Growth Regul 1985;4:120-137.
154. Fitzgerald-Bocarsly P, Feldman M, Mendelsohn M, Curl S, Lopez C. Human mononuclear cells which produce interferon-alpha during NK(HSV-FS) assays are HLA-DR positive cells distinct from cytolytic natural killer effectors. J Leukoc Biol 1988;43:323-334.
155. + blood dendritic cells are potent producers of IFN-alpha in response to in vitro HIV-1 infection. J Immunol 1994;152:4649-4662.
156. Coccia EM, et al. Viral infection and Toll-like receptor agonists induce a differential expression of type I and lambda interferons in human plasmacytoid and monocyte-derived dendritic cells. Eur J Immunol 2004;34:796-805.
157. Kumagai Y, Kumar H, Koyama S, Kawai T, Takeuchi O, Akira S. Cutting edge: TLR-dependent viral recognition along with type I IFN positive feedback signaling masks the requirement of viral replication for IFN-{alpha} production in plasmacytoid dendritic cells. J Immunol 2009;182:3960-3964.
158. Swiecki M, Colonna M. Unraveling the functions of plasmacytoid dendritic cells during viral infections, autoimmunity, and tolerance. Immunol Rev 2010;234:142-162.
159. Cisse B, et al. Transcription factor E2-2 is an essential and specific regulator of plasmacytoid dendritic cell development. Cell 2008;135:37-48.
160. Swiecki M, Gilfillan S, Vermi W, Wang Y, Colonna M. Plasmacytoid dendritic cell ablation impacts early interferon responses and antiviral NK and CD8(+) T cell accrual. Immunity 2010;33:955-966.
161. Nagano Y, Kojima Y. Immunizing property of vaccinia virus inactivated by ultraviolets rays. C R Seances Soc Biol Fil 1954;148:1700-1702.
162. Lindenmann J, Burke DC, Isaacs A. Studies on the production, mode of action and properties of interferon. Br J Exp Pathol 1957;38:551-562.
163. Palucka AK, Blanck JP, Bennett L, Pascual V, Banchereau J. Cross-regulation of TNF and IFN-alpha in autoimmune diseases. Proc Natl Acad Sci USA 2005;102:3372-3377.
164. Ronnblom L, Alm GV, Eloranta ML. The type I interferon system in the development of lupus. Semin Immunol 2011;23:113-121.
165. Ronnblom L, Eloranta ML, Alm GV. Role of natural interferon-alpha producing cells (plasmacytoid dendritic cells) in autoimmunity. Autoimmunity 2003;36:463-472.
166. Fitzgerald-Bocarsly P, Dai J, Singh S. Plasmacytoid dendritic cells and type I IFN: 50years of convergent history. Cytokine Growth Factor Rev 2008;19:3-19.
167. Gilliet M, Lande R. Antimicrobial peptides and self-DNA in autoimmune skin inflammation. Curr Opin Immunol 2008;20:401-407.
168. Ronnblom L, Alm GV, Eloranta ML. Type I interferon and lupus. Curr Opin Rheumatol 2009;21:471-477.
169. Stetson DB. Connections between antiviral defense and autoimmunity. Curr Opin Immunol 2009;21:244-250.
170. Rizvi R, Hojjati M. Interferon-alpha induced lupus in a patient with chronic hepatitis C virus. J Clin Rheumatol 2011;17:152-153.
171. Ronnblom LE, Alm GV, Oberg KE. Possible induction of systemic lupus erythematosus by interferon-alpha treatment in a patient with a malignant carcinoid tumour. J Intern Med 1990;227:207-210.
172. Bonaci-Nikolic B, Jeremic I, Andrejevic S, Sefik-Bukilica M, Stojsavljevic N, Drulovic J. Anti-double stranded DNA and lupus syndrome induced by interferon-beta therapy in a patient with multiple sclerosis. Lupus 2009;18:78-80.
173. Marshak-Rothstein A. Toll-like receptors in systemic autoimmune disease. Nat Rev Immunol 2006;6:823-835.
174. Farkas L, Beiske K, Lund-Johansen F, Brandtzaeg P, Jahnsen FL. Plasmacytoid dendritic cells (natural interferon-alpha/beta producing cells) accumulate in cutaneous lupus erythematosus lesions. Am J Pathol 2001;159:237-243.
175. Sozzani S, Vermi W, Del Prete A, Facchetti F. Trafficking properties of plasmacytoid dendritic cells in health and disease. Trends Immunol 2010;31:270-277.
176. Vermi W, et al. Role of ChemR23 in directing the migration of myeloid and plasmacytoid dendritic cells to lymphoid organs and inflamed skin. J Exp Med 2005;201:509-515.
177. Chen SC, et al. Expression of chemokine receptor CXCR3 by lymphocytes and plasmacytoid dendritic cells in human psoriatic lesions. Arch Dermatol Res 2010;302:113-123.
178. Gerlini G, Mariotti G, Bianchi B, Pimpinelli N. Massive recruitment of type I interferon producing plasmacytoid dendritic cells in varicella skin lesions. J Invest Dermatol 2006;126:507-509.
179. Han GM, Chen SL, Shen N, Ye S, Bao CD, Gu YY. Analysis of gene expression profiles in human systemic lupus erythematosus using oligonucleotide microarray. Genes Immun 2003;4:177-186.
180. Baechler EC, et al. Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus. Proc Natl Acad Sci USA 2003;100:2610-2615.
181. Bennett L, et al. Interferon and granulopoiesis signatures in systemic lupus erythematosus blood. J Exp Med 2003;197:711-723.
182. Crow MK, Kirou KA, Wohlgemuth J. Microarray analysis of interferon-regulated genes in SLE. Autoimmunity 2003;36:481-490.
183. Means TK, et al. Human lupus autoantibody-DNA complexes activate DCs through cooperation of CD32 and TLR9. J Clin Invest 2005;115:407-417.
184. Savarese E, et al. U1 small nuclear ribonucleoprotein immune complexes induce type I interferon in plasmacytoid dendritic cells through TLR7. Blood 2006;107:3229-3234.
185. Garcia-Romo GS, et al. Netting neutrophils are major inducers of type I IFN production in pediatric systemic lupus erythematosus. Sci Transl Med 2011;3:73ra20.
186. Lande R, et al. Neutrophils activate plasmacytoid dendritic cells by releasing self-DNA-peptide complexes in systemic lupus erythematosus. Sci Transl Med 2011;3:73ra19.
187. Lande R, et al. Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide. Nature 2007;449:564-569.
188. Tian J, et al. Toll-like receptor 9-dependent activation by DNA-containing immune complexes is mediated by HMGB1 and RAGE. Nat Immunol 2007;8:487-496.
189. Guiducci C, et al. TLR recognition of self nucleic acids hampers glucocorticoid activity in lupus. Nature 2010;465:937-941.
190. Lepelletier Y, et al. Toll-like receptor control of glucocorticoid-induced apoptosis in human plasmacytoid predendritic cells (pDCs). Blood 2010;116:3389-3397.
191. Albanesi C, et al. Chemerin expression marks early psoriatic skin lesions and correlates with plasmacytoid dendritic cell recruitment. J Exp Med 2009;206:249-258.
192. Nestle FO, et al. Plasmacytoid predendritic cells initiate psoriasis through interferon-alpha production. J Exp Med 2005;202:135-143.
193. Gilliet M, et al. Psoriasis triggered by toll-like receptor 7 agonist imiquimod in the presence of dermal plasmacytoid dendritic cell precursors. Arch Dermatol 2004;140:1490-1495.
194. Stary G, Bangert C, Tauber M, Strohal R, Kopp T, Stingl G. Tumoricidal activity of TLR7/8-activated inflammatory dendritic cells. J Exp Med 2007;204:1441-1451.
195. Vermi W, et al. Spontaneous regression of highly immunogenic molluscum contagiosum virus (MCV)-induced skin lesions is associated with plasmacytoid dendritic cells and IFN-DC infiltration. J Invest Dermatol 2011;131:426-434.
196. Gregorio J, et al. Plasmacytoid dendritic cells sense skin injury and promote wound healing through type I interferons. J Exp Med 2010;207:2921-2930.
197. Guiducci C, et al. Autoimmune skin inflammation is dependent on plasmacytoid dendritic cell activation by nucleic acids via TLR7 and TLR9. J Exp Med 2010;207:2931-2942.
198. Guo B, Chang EY, Cheng G. The type I IFN induction pathway constrains Th17-mediated autoimmune inflammation in mice. J Clin Invest 2008;118:1680-1690.
199. Prinz M, et al. Distinct and nonredundant in vivo functions of IFNAR on myeloid cells limit autoimmunity in the central nervous system. Immunity 2008;28:675-686.
200. Bailey-Bucktrout SL, Caulkins SC, Goings G, Fischer JA, Dzionek A, Miller SD. Cutting edge: central nervous system plasmacytoid dendritic cells regulate the severity of relapsing experimental autoimmune encephalomyelitis. J Immunol 2008;180:6457-6461.
201. Irla M, et al. MHC class II-restricted antigen presentation by plasmacytoid dendritic cells inhibits T cell-mediated autoimmunity. J Exp Med 2010;207:1891-1905.
202. Isaksson M, et al. Plasmacytoid DC promote priming of autoimmune Th17 cells and EAE. Eur J Immunol 2009;39:2925-2935.
203. Bach JF. Insulin-dependent diabetes mellitus as an autoimmune disease. Endocr Rev 1994;15:516-542.
204. Lehuen A, Diana J, Zaccone P, Cooke A. Immune cell crosstalk in type 1 diabetes. Nat Rev Immunol 2010;10:501-513.
205. Guberski DL, et al. Induction of type I diabetes by Kilham's rat virus in diabetes-resistant BB/Wor rats. Science 1991;254:1010-1013.
206. Horwitz MS, Bradley LM, Harbertson J, Krahl T, Lee J, Sarvetnick N. Diabetes induced by Coxsackie virus: initiation by bystander damage and not molecular mimicry. Nat Med 1998;4:781-785.
207. Baek HS, Yoon JW. Direct involvement of macrophages in destruction of beta-cells leading to development of diabetes in virus-infected mice. Diabetes 1991;40:1586-1597.
208. Devendra D, et al. Interferon-alpha as a mediator of polyinosinic:polycytidylic acid-induced type 1 diabetes. Diabetes 2005;54:2549-2556.
209. Moriyama H, et al. Induction and acceleration of insulitis/diabetes in mice with a viral mimic (polyinosinic-polycytidylic acid) and an insulin self-peptide. Proc Natl Acad Sci USA 2002;99:5539-5544.
210. Lang KS, et al. Toll-like receptor engagement converts T-cell autoreactivity into overt autoimmune disease. Nat Med 2005;11:138-145.
211. Castano L, Eisenbarth GS. Type-I diabetes: a chronic autoimmune disease of human, mouse, and rat. Annu Rev Immunol 1990;8:647-679.
212. Stewart TA, Hultgren B, Huang X, Pitts-Meek S, Hully J, MacLachlan NJ. Induction of type I diabetes by interferon-alpha in transgenic mice. Science 1993;260:1942-1946.
213. Li Q, Xu B, Michie SA, Rubins KH, Schreriber RD, McDevitt HO. Interferon-alpha initiates type 1 diabetes in nonobese diabetic mice. Proc Natl Acad Sci USA 2008;105:12439-12444.
214. Li Q, McDevitt HO. The role of interferon alpha in initiation of type I diabetes in the NOD mouse. Clin Immunol 2011;140:3-7.
215. Allen JS, et al. Plasmacytoid dendritic cells are proportionally expanded at diagnosis of type 1 diabetes and enhance islet autoantigen presentation to T-cells through immune complex capture. Diabetes 2009;58:138-145.
216. Smith KA, Efstathiou S, Cooke A. Murine gammaherpesvirus-68 infection alters self-antigen presentation and type 1 diabetes onset in NOD mice. J Immunol 2007;179:7325-7333.
217. Feillet H, Bach JF. On the mechanisms of the protective effect of infections on type 1 diabetes. Clin Dev Immunol 2004;11:191-194.
218. Filippi CM, Estes EA, Oldham JE, von Herrath MG. Immunoregulatory mechanisms triggered by viral infections protect from type 1 diabetes in mice. J Clin Invest 2009;119:1515-1523.
219. Boettler T, von Herrath M. Protection against or triggering of Type 1 diabetes? Different roles for viral infections. Expert Rev Clin Immunol 2011;7:45-53.
220. Diana J, et al. NKT cell-plasmacytoid dendritic cell cooperation via OX40 controls viral infection in a tissue-specific manner. Immunity 2009;30:289-299.
221. Diana J, et al. Viral infection prevents diabetes by inducing regulatory T cells through NKT cell-plasmacytoid dendritic cell interplay. J Exp Med 2010;208:729-745.
222. Serreze DV, Hamaguchi K, Leiter EH. Immunostimulation circumvents diabetes in NOD/Lt mice. J Autoimmun 1989;2:759-776.
223. Tanaka-Kataoka M, et al. Oral use of interferon-alpha delays the onset of insulin-dependent diabetes mellitus in nonobese diabetes mice. J Interferon Cytokine Res 1999;19:877-879.
224. Sobel DO, Ahvazi B. Alpha-interferon inhibits the development of diabetes in NOD mice. Diabetes 1998;47:1867-1872.
225. von Herrath M. Diabetes: a virus-gene collaboration. Nature 2009;459:518-519.
226. Nejentsev S, Walker N, Riches D, Egholm M, Todd JA. Rare variants of IFIH1, a gene implicated in antiviral responses, protect against type 1 diabetes. Science 2009;324:387-389.
227. Smyth DJ, et al. A genome-wide association study of nonsynonymous SNPs identifies a type 1 diabetes locus in the interferon-induced helicase (IFIH1) region. Nat Genet 2006;38:617-619.
228. Shigemoto T, Kageyama M, Hirai R, Zheng J, Yoneyama M, Fujita T. Identification of loss of function mutations in human genes encoding RIG-I and MDA5: implications for resistance to type I diabetes. J Biol Chem 2009;284:13348-13354.
229. Downes K, et al. Reduced expression of IFIH1 is protective for type 1 diabetes. PLoS ONE 2010;5:e12646.
230. Louten J, van Rooijen N, Biron CA. Type 1 IFN deficiency in the absence of normal splenic architecture during lymphocytic choriomeningitis virus infection. J Immunol 2006;177:3266-3272.
231. Lang PA, et al. Tissue macrophages suppress viral replication and prevent severe immunopathology in an interferon-I-dependent manner in mice. Hepatology 2010;52:25-32.
232. Jung A, et al. Lymphocytoid choriomeningitis virus activates plasmacytoid dendritic cells and induces a cytotoxic T-cell response via MyD88. J Virol 2008;82:196-206.
233. Zhou S, Cerny AM, Zacharia A, Fitzgerald KA, Kurt-Jones EA, Finberg RW. Induction and inhibition of type I interferon responses by distinct components of lymphocytic choriomeningitis virus. J Virol 2010;84:9452-9462.
234. Wang T, Town T, Alexopoulou L, Anderson JF, Fikrig E, Flavell RA. Toll-like receptor 3 mediates West Nile virus entry into the brain causing lethal encephalitis. Nat Med 2004;10:1366-1373.
235. Daffis S, Samuel MA, Suthar MS, Gale M Jr, Diamond MS. Toll-like receptor 3 has a protective role against West Nile virus infection. J Virol 2008;82:10349-10358.
236. Tabeta K, 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.
237. Wang Q, et al. Role of double-stranded RNA pattern recognition receptors in rhinovirus-induced airway epithelial cell responses. J Immunol 2009;183:6989-6997.
238. Slater L, et al. Co-ordinated role of TLR3, RIG-I and MDA5 in the innate response to rhinovirus in bronchial epithelium. PLoS Pathog 2010;6:e1001178.
239. Nasirudeen AM, Wong HH, Thien P, Xu S, Lam KP, Liu DX. RIG-I, MDA5 and TLR3 synergistically play an important role in restriction of dengue virus infection. PLoS Negl Trop Dis 2011;5:e926.
240. Beignon AS, et al. Endocytosis of HIV-1 activates plasmacytoid dendritic cells via Toll-like receptor-viral RNA interactions. J Clin Invest 2005;115:3265-3275.
241. Wang JP, Asher DR, Chan M, Kurt-Jones EA, Finberg RW. Cutting edge: antibody-mediated TLR7-dependent recognition of viral RNA. J Immunol 2007;178:3363-3367.
242. Davidson S, et al. Plasmacytoid dendritic cells promote host defense against acute pneumovirus infection via the TLR7-MyD88-dependent signaling pathway. J Immunol 2011;186:5938-5948.
243. Krug A, et al. TLR9-dependent recognition of MCMV by IPC and DC generates coordinated cytokine responses that activate antiviral NK cell function. Immunity 2004;21:107-119.
244. Krug A, Luker GD, Barchet W, Leib DA, Akira S, Colonna M. Herpes simplex virus type 1 activates murine natural interferon-producing cells through toll-like receptor 9. Blood 2004;103:1433-1437.
245. Lund J, Sato A, Akira S, Medzhitov R, Iwasaki A. Toll-like receptor 9-mediated recognition of Herpes simplex virus-2 by plasmacytoid dendritic cells. J Exp Med 2003;198:513-520.
246. Fiola S, Gosselin D, Takada K, Gosselin J. TLR9 contributes to the recognition of EBV by primary monocytes and plasmacytoid dendritic cells. J Immunol 2010;185:3620-3631.
247. Yoneyama M, et al. Shared and unique functions of the DExD/H-box helicases RIG-I, MDA5, and LGP2 in antiviral innate immunity. J Immunol 2005;175:2851-2858.
248. Yoboua F, Martel A, Duval A, Mukawera E, Grandvaux N. Respiratory syncytial virus-mediated NF-kappa B p65 phosphorylation at serine 536 is dependent on RIG-I, TRAF6, and IKK beta. J Virol 2010;84:7267-7277.
249. Ikegame S, Takeda M, Ohno S, Nakatsu Y, Nakanishi Y, Yanagi Y. Both RIG-I and MDA5 RNA helicases contribute to the induction of alpha/beta interferon in measles virus-infected human cells. J Virol 2010;84:372-379.
250. Plumet S, Herschke F, Bourhis JM, Valentin H, Longhi S, Gerlier D. Cytosolic 5'-triphosphate ended viral leader transcript of measles virus as activator of the RIG I-mediated interferon response. PLoS ONE 2007;2:e279.
251. Hornung V, et al. 5'-Triphosphate RNA is the ligand for RIG-I. Science 2006;314:994-997.
252. Fredericksen BL, Gale M Jr. West Nile virus evades activation of interferon regulatory factor 3 through RIG-I-dependent and -independent pathways without antagonizing host defense signaling. J Virol 2006;80:2913-2923.
253. McCartney SA, Thackray LB, Gitlin L, Gilfillan S, Virgin HW, Colonna M. MDA-5 recognition of a murine norovirus. PLoS Pathog 2008;4:e1000108.
254. Roth-Cross JK, Bender SJ, Weiss SR. Murine coronavirus mouse hepatitis virus is recognized by MDA5 and induces type I interferon in brain macrophages/microglia. J Virol 2008;82:9829-9838.
255. Melchjorsen J, et al. Early innate recognition of herpes simplex virus in human primary macrophages is mediated via the MDA5/MAVS-dependent and MDA5/MAVS/RNA polymerase III-independent pathways. J Virol 2010;84:11350-11358.
256. Calderon B, Suri A, Miller MJ, Unanue ER. Dendritic cells in islets of Langerhans constitutively present beta cell-derived peptides bound to their class II MHC molecules. Proc Natl Acad Sci USA 2008;105:6121-6126.
257. Colisson R, et al. Free HLTV-1 induces TLR7-dependent innate immune response and TRAIL relocalization in killer plasmacytoid dendritic cells. Blood 2010;115:2177-2185.
258. Cervantes-Barragan L, et al. Control of coronavirus infection through plasmacytoid dendritic-cell-derived type I interferon. Blood 2007;109:1131-1137.