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

doi:10.1371/journal.ppat.1005754

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

Journal article

Open access

Peer reviewed

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 and Balaji Manicassamy

PLoS pathogens, Vol.12(7), pp.e1005754-e1005754

07/2016

DOI: 10.1371/journal.ppat.1005754

PMCID: PMC4954706

PMID: 27438481

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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.

Flow Cytometry

Polymerase Chain Reaction

Nerve Tissue Proteins - immunology

Coculture Techniques

Dendritic Cells - immunology

Membrane Proteins - immunology

Interferon Type I - immunology

Mice, Knockout

Nerve Tissue Proteins - metabolism

Interferon Type I - biosynthesis

Signal Transduction - immunology

Lymphocyte Activation - immunology

Animals

T-Lymphocytes - metabolism

Adaptor Proteins, Signal Transducing - immunology

Influenza A virus - immunology

T-Lymphocytes - immunology

Membrane Proteins - metabolism

Mice

Orthomyxoviridae Infections - immunology

Disease Models, Animal

Details

Title: Subtitle: RIG-I Signaling Is Critical for Efficient Polyfunctional T Cell Responses during Influenza Virus Infection
Creators: Matheswaran Kandasamy - Department of Microbiology, The University of Chicago, Chicago, Illinois, United States of America
Amol Suryawanshi - Cancer Immunology, Inflammation, and Tolerance Program, GRU Cancer Center, Georgia Regents University, Augusta, Georgia, United States of America
Smanla Tundup - Department of Microbiology, The University of Chicago, Chicago, Illinois, United States of America
Jasmine T Perez - Department of Microbiology, The University of Chicago, Chicago, Illinois, United States of America
Mirco Schmolke - Department of Microbiology and Molecular Medicine, University of Geneva Medical Faculty, CMU, Geneva, Switzerland
Santhakumar Manicassamy - Cancer Immunology, Inflammation, and Tolerance Program, GRU Cancer Center, Georgia Regents University, Augusta, Georgia, United States of America
Balaji Manicassamy - Department of Microbiology, The University of Chicago, Chicago, Illinois, United States of America
Resource Type: Journal article
Publication Details: PLoS pathogens, Vol.12(7), pp.e1005754-e1005754
DOI: 10.1371/journal.ppat.1005754
PMID: 27438481
PMCID: PMC4954706
NLM abbreviation: PLoS Pathog
ISSN: 1553-7366
eISSN: 1553-7374
Publisher: Public Library of Science
Grant note: R01 DK097271 / NIDDK NIH HHS
Language: English
Date published: 07/2016
Academic Unit: Microbiology and Immunology
Record Identifier: 9984083278302771

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