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.

中文翻译：

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NLRC5缺乏症对成年小鼠轮状病毒感染过程中免疫优势CD8 + T细胞反应的影响中等。

NOD样受体（NLR）家族在先天免疫中起重要作用。II类反式激活因子和NOD样受体胱天蛋白酶激活和募集结构域CARD包含5（NLRC5）是NLR家族的不常见成员，它们不识别病原体相关或损伤相关的分子模式，而是与衔接子分子形成增强体并调节主要的组织相容性复合体（MHC）II类和MHC I类表达。尽管已显示NLRC5在细胞内病原体感染和肿瘤细胞免疫逃逸过程中发挥作用，但尚未研究其在肠道粘膜调节抗原特异性CD8 + T细胞反应中的作用。在这里，我们利用成年小鼠轮状病毒模型来剖析NLRC5对肠道粘膜对该病毒感染的CD8 + T细胞反应的影响。我们显示，虽然Nlrc5-/-小鼠在上皮内和固有层隔室中显示正常比例的T细胞亚群，但这些小鼠在固有层中的各种免疫细胞上均降低了基线MHC I类表达。轮状病毒感染后，Nlrc5缺乏症会导致H2-Kb限制性抗原特异性CD8 + T细胞反应受损，在树突状细胞区室中缺乏Nlrc5的小鼠中重新概括。Nlrc5-/-小鼠中CD8 + T细胞应答受损不足以影响病毒滴度，表明Nlrc5-/-小鼠中存在补偿，这可能是由于肠系膜淋巴结和正常轮状病毒中激活的B细胞数量增加所致特异性免疫球蛋白A反应。总的来说，