RIG-I Signaling Is Critical for Efficient Polyfunctional T Cell Responses during Influenza Virus Infection.
RIG-I Signaling Is Critical for Efficient Polyfunctional T Cell Responses during Influenza Virus Infection.
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DOI：
10.1371/journal.ppat.1005754
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发表时间：
2016-07
期刊：
影响因子：
6.7
通讯作者：
Manicassamy B
中科院分区：
文献类型：
--
作者：
Kandasamy M;Suryawanshi A;Tundup S;Perez JT;Schmolke M;Manicassamy S;Manicassamy B
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. Retinoic acid inducible gene-I (RIG-I) is a cytosolic RNA sensor that detects influenza virus infection and has been previously shown to be critical for controlling influenza virus replication in cell culture systems. Here, we performed studies in mice with defects in the RIG-I pathway to understand its role in initiating immune responses against influenza virus. Our studies show that RIG-I signaling protects host lung tissue from influenza virus infection and aids in the timely clearance of influenza virus from the lungs. Consistent with this observation, RIG-I deficient mice show defects in type I IFN production and subsequent activation of the adaptive immune response (T cell responses) against influenza viruses. This defect in T cell activation is overcome by exogenous addition of type I IFN to antigen presenting cells (APC) in vitro or by poly I:C treatment of RIG-I deficient mice, demonstrating that RIG-I signaling is critical for type I IFN production and proper activation of adaptive responses against influenza virus infection. Thus, our study suggests that RIG-I signaling is essential for reducing influenza virus disease burden in a timely manner and for providing protection against emerging novel IAV strains.
