RIG-I Signaling Is Critical for Efficient Polyfunctional T Cell Responses during Influenza Virus Infection

Matheswaran Kandasamy, Amol Suryawanshi, Smanla Tundup, Jasmine T. Perez, Mirco Schmolke, Santhakumar Manicassamy, Balaji Manicassamy

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Retinoic acid inducible gene-I (RIG-I) is an innate RNA sensor that recognizes the influenza A virus (IAV) RNA genome and activates antiviral host responses. Here, we demonstrate that RIG-I signaling plays a crucial role in restricting IAV tropism and regulating host immune responses. Mice deficient in the RIG-I-MAVS pathway show defects in migratory dendritic cell (DC) activation, viral antigen presentation, and priming of CD8+ and CD4+ T cell responses during IAV infection. These defects result in decreased frequency of polyfunctional effector T cells and lowered protection against heterologous IAV challenge. In addition, our data show that RIG-I activation is essential for protecting epithelial cells and hematopoietic cells from IAV infection. These diverse effects of RIG-I signaling are likely imparted by the actions of type I interferon (IFN), as addition of exogenous type I IFN is sufficient to overcome the defects in antigen presentation by RIG-I deficient BMDC. Moreover, the in vivo T cell defects in RIG-I deficient mice can be overcome by the activation of MDA5 –MAVS via poly I:C treatment. Taken together, these findings demonstrate that RIG-I signaling through MAVS is critical for determining the quality of polyfunctional T cell responses against IAV and for providing protection against subsequent infection from heterologous or novel pandemic IAV strains.

Original languageEnglish (US)
Article numbere1005754
JournalPLoS Pathogens
Volume12
Issue number7
DOIs
StatePublished - Jul 2016

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

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    Kandasamy, M., Suryawanshi, A., Tundup, S., Perez, J. T., Schmolke, M., Manicassamy, S., & Manicassamy, B. (2016). RIG-I Signaling Is Critical for Efficient Polyfunctional T Cell Responses during Influenza Virus Infection. PLoS Pathogens, 12(7), [e1005754]. https://doi.org/10.1371/journal.ppat.1005754