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 MNV ^CR6是人类诺如病毒和肠道病毒持久性的模型。 MNV ^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。尽管 MNV ^CR6诱导功能性 MNV 特异性 CD8 ⁺ T 细胞，但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，我们通过将 JEDI（仅诱导 EGFP 死亡）CD8 ⁺ T 细胞过继转移至 Gfi1b-GFP 簇细胞报告小鼠体内，研究簇细胞与 CD8 ⁺ T 细胞的相互作用。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 ⁺肠道干细胞和肠外簇细胞不同——尽管表面上抗原呈递正常。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。 JEDI CD8 ⁺ T 细胞既不能清除也不能阻止结肠（病毒持续存在的部位）中的MNV ^CR6感染，尽管其目标是独立于病毒的抗原。最终，我们发现肠道簇细胞对 CD8 ⁺ T 细胞具有相对抵抗力，与诺如病毒感染无关，代表了肠道微生物可以利用的免疫特权生态位。