MAVS and MyD88 are essential for innate immunity but not cytotoxic T lymphocyte response against respiratory syncytial virus

Vijay G. Bhoj, Qinmiao Sun, Elizabeth J. Bhoj, Cynthia Somers, Xiang Chen, Juan Pablo Torres, Asuncion Mejias, Ana M. Gomez, Hasan Jafri, Octavio Ramilo, Zhijian J. Chen

Research output: Contribution to journalArticle

99 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)14046-14051
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number37
DOIs
StatePublished - Sep 16 2008

Keywords

  • Adaptive immunity
  • IFN
  • RSV

ASJC Scopus subject areas

  • General

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