NLRC5 deficiency has a moderate impact on immunodominant CD CD 8 + + T‐cell responses during rotavirus infection of adult mice

摘要

Abstract The NOD ‐like receptor ( NLR ) family plays an important role in innate immunity. Class II transactivator and NOD‐like receptor caspase activation and recruitment domain CARD containing 5 (NLRC5) are unusual members of the NLR family that instead of recognizing pathogen‐associated or damage‐associated molecular patterns, form enhanceosomes with adaptor molecules and modulate major histocompatibility complex ( MHC ) class II and MHC class I expression, respectively. While NLRC 5 has been shown to play a role during intracellular pathogen infection and tumor cell immune evasion, its role in regulating antigen‐specific CD 8 + T‐cell responses at the intestinal mucosa has not been investigated. Here, we take advantage of the rotavirus model in adult mice to dissect the impact of NLRC 5 on CD 8 + T‐cell responses to this viral infection at the gut mucosa. We show that while Nlrc5 ?/? mice exhibited normal proportions of T‐cell subpopulations in the intraepithelial and lamina propria compartments, these mice had decreased baseline MHC class I expression on various immune cells in the lamina propria. Upon rotavirus infection, Nlrc5 deficiency resulted in impaired H2‐K b ‐restricted antigen‐specific CD 8 + T‐cell responses, which were recapitulated in mice deficient for Nlrc5 within the dendritic cell compartment. The impaired CD 8 + T‐cell response in Nlrc5 ?/? mice was not significant enough to impact viral titers, suggesting compensation in Nlrc5 ?/? mice, perhaps as a result of higher numbers of activated B cells in the mesenteric lymph nodes and normal rotavirus‐specific immunoglobulin A responses. Collectively, our results demonstrate a minor role for NLRC 5 in modulating H2‐K b ‐restricted antigen‐specific CD 8 + T‐cell responses in the small intestine during rotavirus infection in adult mice.