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

Immunol Cell Biol. 2019 Jul;97(6):552-562. doi: 10.1111/imcb.12244. Epub 2019 Mar 29.

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-Kb -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-Kb -restricted antigen-specific CD8+ T-cell responses in the small intestine during rotavirus infection in adult mice.

Keywords: Adaptive immunity; MHC-I; NLRC5, rotavirus; dendritic cells; small intestine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation
  • Antigens, Viral / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cells, Cultured
  • Dendritic Cells / immunology*
  • H-2 Antigens / metabolism
  • Immunodominant Epitopes / immunology
  • Intestinal Mucosa / immunology*
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Rotavirus / physiology*
  • Rotavirus Infections / immunology*
  • Viral Load

Substances

  • Antigens, Viral
  • H-2 Antigens
  • H-2Kb protein, mouse
  • Immunodominant Epitopes
  • Intracellular Signaling Peptides and Proteins
  • NLRC5 protein, mouse