Deficiency of the NOD-Like Receptor NLRC5 Results in Decreased CD8+ T Cell Function and Impaired Viral Clearance.

Abstract

Pathogen recognition receptors are vital components of the immune system. Engagement of these receptors is important not only for instigation of innate immune responses to invading pathogens but also for initiating the adaptive immune response. Members of the NOD-like receptor (NLR) family of pathogen recognition receptors have important roles in orchestrating this response. The NLR family member NLRC5 regulates major histocompatibility complex class I (MHC-I) expression during various types of infections, but its role in immunity to influenza A virus (IAV) is not well studied. Here we show that Nlrc5-/- mice exhibit an altered CD8+ T cell response during IAV infection compared to that of wild-type (WT) mice. Nlrc5-/- mice have decreased MHC-I expression on hematopoietic cells and fewer CD8+ T cells prior to infection. NLRC5 deficiency does not affect the generation of antigen-specific CD8+ T cells following IAV infection; however, a change in epitope dominance is observed in Nlrc5-/- mice. Moreover, IAV-specific CD8+ T cells from Nlrc5-/- mice have impaired effector functions. This change in the adaptive immune response is associated with impaired viral clearance in Nlrc5-/- mice. Collectively, our results demonstrate an important role for NLRC5 in regulation of antiviral immune responses and viral clearance during IAV infection.

Department(s)

Biology

Document Type

Article

DOI

https://doi.org/10.1128/jvi.00377-17

Keywords

nod-like receptor, NLR, NLRC5, influenza A virus, lung, T cellmajor histocompatibility complex, MHC, natural killer cell

Publication Date

2017

Journal Title

Journal of Virology

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