NLRC5 deficiency has a moderate impact on immunodominant CD8 + T-cell responses during rotavirus infection of adult mice

Tian Sun, Richard L. Ferrero, Stephen E. Girardin, Jennifer L. Gommerman, Dana J. Philpott

Research output: Contribution to journalArticleResearchpeer-review

5 Citations (Scopus)

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 NLRC5 has been shown to play a role during intracellular pathogen infection and tumor cell immune evasion, its role in regulating antigen-specific CD8 + 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 NLRC5 on CD8 + 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 CD8 + T-cell responses, which were recapitulated in mice deficient for Nlrc5 within the dendritic cell compartment. The impaired CD8 + 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 NLRC5 in modulating H2-K b -restricted antigen-specific CD8 + T-cell responses in the small intestine during rotavirus infection in adult mice.

Original languageEnglish
Pages (from-to)552-562
Number of pages11
JournalImmunology and Cell Biology
Volume97
Issue number6
DOIs
Publication statusPublished - Jul 2019

Keywords

  • Adaptive immunity
  • dendritic cells
  • MHC-I
  • NLRC5, rotavirus
  • small intestine

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