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.

Nanoplasmid Vectors Co-expressing Innate Immune Agonists Enhance DNA Vaccines for Venezuelan Equine Encephalitis Virus and Ebola Virus

“…Instead, it appears that the inclusion of the isRNA innate immune agonist had the greatest influence on vaccine immunogenicity. Despite the importance of RIG-I signaling in generating antigen-specific T cells, 34 we did not measure a significant increase in the numbers of IFN-g + or IL-2 + T cells for either antigen. This is in agreement with previous findings that the isRNA expression did not enrich T cell immunity, possibly due to the lack of a hairpin structure in the dsRNA transcribed from the Nanoplasmids.…”

MCPIP1 attenuates the innate immune response to influenza A virus by suppressing RIG‐I expression in lung epithelial cells

“…RIG‐I is an innate sensor and direct antiviral factor against IAV infection. Inhibition of RIG‐I certainly impairs type I IFN production, immune cell activation and stimulation of the adaptive immune system . These results suggest that IAV‐induced MCPIP1 is not only involved in antiviral effects, but in controlling RIG‐I signaling, which is beneficial to the virus at later times of infection.…”

“…Within the cytosol of IAV‐infected epithelial cells, RIG‐I recognizes and binds to the 5′‐triphosphate with blunt‐ended double‐stranded RNA component as contained in panhandle of the IAV genome, which then binds to its downstream adaptor molecule mitochondrial antiviral signaling protein (MAVS) . Upon its activation, RIG‐I/MAVS induces the activation of transcription factor interferon (IFN) regulatory factor (IRF) 3 and NF‐κB, ultimately resulting in establishing an antiviral state against IAV in the host cells through both type I IFN production and efficient polyfunctional T cell responses …”

“…the host cells through both type I IFN production and efficient polyfunctional T cell responses. 9,10 The monocyte chemotactic protein-induced protein 1 (MCPIP1) is originally described as a gene induced by MCP-1. 11 A growing body of evidence suggests that the RNase and deubiquitinase (DUB) activities of MCPIP1 are involved in various biological processes.…”

The self‐curing phenomenon of schistosome infection in rhesus macaques: insight from in vitro studies

“…These findings suggest that multifunctional cellular immune responses might be involved in the self‐cure process. Several studies have demonstrated the protective roles of host polyfunctional cells against numerous infectious organisms . For example, the frequency of Plasmodium falciparium ‐specific polyfunctional T cells has been associated with protection in humans .…”