title: MAVS and MyD88 are essential for innate immunity but not cytotoxic T lymphocyte response against respiratory syncytial virus.
abstract: Infection by RNA viruses is detected by the host through Toll-like receptors or RIG-I-like receptors. Toll-like receptors and RIG-I-like receptors signal through the adaptors MyD88 and MAVS, respectively, to induce type I IFNs (IFN-I) and other antiviral molecules, which are thought to be essential for activating the adaptive immune system. We investigated the role of these adaptors in innate and adaptive immune responses against respiratory syncytial virus (RSV), a common human pathogen. Deletion of Mavs abolished the induction of IFN-I and other proinflammatory cytokines by RSV. Genome-wide expression profiling in the lung showed that the vast majority of RSV-induced genes depended on MAVS. Although Myd88 deficiency did not affect most RSV-induced genes, mice lacking both adaptors harbored a higher and more prolonged viral load and exhibited more severe pulmonary disease than those lacking either adaptor alone. Surprisingly, Myd88(-/-)Mavs(-/-) mice were able to activate a subset of pulmonary dendritic cells that traffic to the draining lymph node in response to RSV. These mice subsequently mounted a normal cytotoxic T-lymphocyte response and demonstrated delayed but effective viral clearance. These results provide an example of a normal and effective adaptive immune response in the absence of innate immunity mediated by MAVS and MyD88.
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA.
authors.forename: Vijay G
authors.initials: VG
authors.lastname: Bhoj
authors.forename: Qinmiao
authors.initials: Q
authors.lastname: Sun
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Bhoj
authors.forename: Cynthia
authors.initials: C
authors.lastname: Somers
authors.forename: Xiang
authors.initials: X
authors.lastname: Chen
authors.forename: Juan-Pablo
authors.initials: JP
authors.lastname: Torres
authors.forename: Asuncion
authors.initials: A
authors.lastname: Mejias
authors.forename: Ana M
authors.initials: AM
authors.lastname: Gomez
authors.forename: Hasan
authors.initials: H
authors.lastname: Jafri
authors.forename: Octavio
authors.initials: O
authors.lastname: Ramilo
authors.forename: Zhijian J
authors.initials: ZJ
authors.lastname: Chen
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D005786:Gene Expression Regulation; D007113:Immunity, Innate / Q000276:immunology*; D008171:Lung Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018357:Respiratory Syncytial Virus Infections / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D016207:Cytokines; D053594:Myeloid Differentiation Factor 88; C512612:MAVS protein, mouse
references.citation: J Exp Med. 2006 May 15;203(5):1153-9
references.pmid: 16682497
references.citation: Virology. 2005 Jul 5;337(2):335-43
references.pmid: 15916793
references.citation: Proc Am Thorac Soc. 2005;2(2):166-73
references.pmid: 16113487
references.citation: Cell. 2006 Feb 24;124(4):783-801
references.pmid: 16497588
references.citation: Immunity. 2007 Sep;27(3):370-83
references.pmid: 17892846
references.citation: Science. 2006 Nov 10;314(5801):994-7
references.pmid: 17038590
references.citation: J Clin Invest. 1991 Sep;88(3):1026-33
references.pmid: 1909350
references.citation: Cell Res. 2006 Feb;16(2):141-7
references.pmid: 16474426
references.citation: Nat Immunol. 2004 Oct;5(10):971-4
references.pmid: 15454919
references.citation: Nature. 1998 Mar 19;392(6673):245-52
references.pmid: 9521319
references.citation: Immunity. 2005 Jul;23(1):19-28
references.pmid: 16039576
references.citation: Mol Cell. 2005 Sep 16;19(6):727-40
references.pmid: 16153868
references.citation: Proc Am Thorac Soc. 2005;2(2):121-5
references.pmid: 16113479
references.citation: J Immunol. 1999 Apr 1;162(7):4207-11
references.pmid: 10201948
references.citation: Cold Spring Harb Symp Quant Biol. 1999;64:429-35
references.pmid: 11232318
references.citation: Cell. 2005 Sep 9;122(5):669-82
references.pmid: 16125763
references.citation: Pediatr Infect Dis J. 2003 Feb;22(2 Suppl):S13-8; discussion S18-20
references.pmid: 12671448
references.citation: Antivir Ther. 2007;12(4 Pt B):659-70
references.pmid: 17944273
references.citation: Nat Immunol. 2005 Oct;6(10):981-8
references.pmid: 16127453
references.citation: Science. 2006 Nov 10;314(5801):997-1001
references.pmid: 17038589
references.citation: Nature. 2005 Feb 24;433(7028):887-92
references.pmid: 15711573
references.citation: Immunity. 2007 Aug;27(2):240-52
references.pmid: 17723216
references.citation: J Infect Dis. 2004 May 15;189(10):1856-65
references.pmid: 15122522
references.citation: Immunity. 2006 May;24(5):633-42
references.pmid: 16713980
references.citation: J Immunol. 2007 Oct 1;179(7):4711-20
references.pmid: 17878370
references.citation: J Immunol. 2007 May 1;178(9):5820-7
references.pmid: 17442966
references.citation: J Virol. 2007 Sep;81(18):9790-800
references.pmid: 17626092
references.citation: J Virol. 2008 Jan;82(1):196-206
references.pmid: 17942529
references.citation: Nature. 2005 Oct 20;437(7062):1167-72
references.pmid: 16177806
references.citation: J Immunol. 2006 Nov 1;177(9):6263-70
references.pmid: 17056556
references.citation: J Pediatr. 2003 Nov;143(5 Suppl):S112-7
references.pmid: 14615709