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

PLoS Pathogens

Amol Suryawanshi¹  Santhakumar Manicassamy¹  Mirco Schmolke²  Matheswaran Kandasamy³  Jasmine T. Perez³  Balaji Manicassamy³  Smanla Tundup³ 

[1] Cancer Immunology, Inflammation, and Tolerance Program, GRU Cancer Center, Georgia Regents University, Augusta, Georgia, United States of America;Department of Microbiology and Molecular Medicine, University of Geneva Medical Faculty, CMU, Geneva, Switzerland;Department of Microbiology, The University of Chicago, Chicago, Illinois, United States of America

关键词: T cells;    Cytotoxic T cells;    Influenza A virus;    Respiratory infections;    Flow cytometry;    Cell staining;    Antigen presentation;    Interferons;   

DOI  :  10.1371/journal.ppat.1005754

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY