The persistent murine norovirus strain MNV CR6 is a model for human norovirus and enteric viral persistence. MNV CR6 causes chronic infection by directly infecting intestinal tuft cells, rare chemosensory epithelial cells. Although MNV CR6 induces functional MNV-specific CD8 + T cells, these lymphocytes fail to clear infection. To examine how tuft cells promote immune escape, we interrogated tuft cell interactions with CD8 + T cells by adoptively transferring JEDI (just EGFP death inducing) CD8 + T cells into Gfi1b-GFP tuft cell reporter mice. Unexpectedly, some intestinal tuft cells partially resisted JEDI CD8 + T cell–mediated killing—unlike Lgr5 + intestinal stem cells and extraintestinal tuft cells—despite seemingly normal antigen presentation. When targeting intestinal tuft cells, JEDI CD8 + T cells predominantly adopted a T resident memory phenotype with decreased effector and cytotoxic capacity, enabling tuft cell survival. JEDI CD8 + T cells neither cleared nor prevented MNV CR6 infection in the colon, the site of viral persistence, despite targeting a virus-independent antigen. Ultimately, we show that intestinal tuft cells are relatively resistant to CD8 + T cells independent of norovirus infection, representing an immune-privileged niche that can be leveraged by enteric microbes.

中文翻译：

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肠道簇细胞免疫特权使诺如病毒能够持久存在

持久性鼠诺如病毒株MNVCR6是人类诺如病毒和肠道病毒持久性的模型。微血管病毒CR6通过直接感染肠道簇细胞（罕见的化学感应上皮细胞）引起慢性感染。虽然MNVCR6诱导功能性 MNV 特异性 CD8+T 细胞，这些淋巴细胞无法清除感染。为了研究簇细胞如何促进免疫逃逸，我们研究了簇细胞与 CD8 的相互作用+通过过继转移 JEDI（仅诱导 EGFP 死亡）CD8 的 T 细胞+T 细胞注入 Gfi1b-GFP 簇细胞报告小鼠。出乎意料的是，一些肠道簇细胞部分抵抗了 JEDI CD8+T 细胞介导的杀伤——与 Lgr5 不同+肠干细胞和肠外簇状细胞——尽管抗原呈递看似正常。当靶向肠道簇细胞时，JEDI CD8+T细胞主要采用T驻留记忆表型，效应子和细胞毒性能力降低，从而使簇细胞能够存活。绝地CD8+T 细胞既不能清除也不能预防 MNVCR6尽管针对的是独立于病毒的抗原，但结肠中的感染是病毒持续存在的部位。最终，我们证明肠道簇细胞对 CD8 具有相对抵抗力+独立于诺如病毒感染的 T 细胞，代表了肠道微生物可以利用的免疫特权生态位。