title: RIG-I Signaling Is Critical for Efficient Polyfunctional T Cell Responses during Influenza Virus Infection.
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.
authors.affiliation: Department of Microbiology, The University of Chicago, Chicago, Illinois, United States of America.
authors.forename: Matheswaran
authors.initials: M
authors.lastname: Kandasamy
authors.affiliation: Cancer Immunology, Inflammation, and Tolerance Program, GRU Cancer Center, Georgia Regents University, Augusta, Georgia, United States of America.
authors.forename: Amol
authors.initials: A
authors.lastname: Suryawanshi
authors.affiliation: Department of Microbiology, The University of Chicago, Chicago, Illinois, United States of America.
authors.forename: Smanla
authors.initials: S
authors.lastname: Tundup
authors.affiliation: Department of Microbiology, The University of Chicago, Chicago, Illinois, United States of America.
authors.forename: Jasmine T
authors.initials: JT
authors.lastname: Perez
authors.affiliation: Department of Microbiology and Molecular Medicine, University of Geneva Medical Faculty, CMU, Geneva, Switzerland.
authors.forename: Mirco
authors.initials: M
authors.lastname: Schmolke
authors.affiliation: Cancer Immunology, Inflammation, and Tolerance Program, GRU Cancer Center, Georgia Regents University, Augusta, Georgia, United States of America.
authors.forename: Santhakumar
authors.initials: S
authors.lastname: Manicassamy
authors.affiliation: Department of Microbiology, The University of Chicago, Chicago, Illinois, United States of America.
authors.forename: Balaji
authors.initials: B
authors.lastname: Manicassamy
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology; D000818:Animals; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology; D004195:Disease Models, Animal; D005434:Flow Cytometry; D009980:Influenza A virus / Q000276:immunology; D007370:Interferon Type I / Q000096:biosynthesis / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008565:Membrane Proteins / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000276:immunology* / Q000378:metabolism; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D016133:Polymerase Chain Reaction; D011956:Receptors, Cell Surface; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D000097905:Roundabout Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D007370:Interferon Type I; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface; C512612:MAVS protein, mouse; C118348:Robo3 protein, mouse; D000097905:Roundabout Proteins