Key Points MHC I can be induced in skeletal muscle in a doxycycline dose–dependent manner. Elevated muscle MHC I results in initial enhanced immune control of Trypanosoma cruzi. Sustained elevation in muscle MHC I ultimately exhausts pathogen-specific responses. Myocytes express low levels of MHC class I (MHC I), perhaps influencing the ability of CD8+ T cells to efficiently detect and destroy pathogens that invade muscle. Trypanosoma cruzi infects many cell types but preferentially persists in muscle, and we asked if this tissue-dependent persistence was linked to MHC expression. Inducible enhancement of skeletal muscle MHC I in mice during the first 20 d of T. cruzi infection resulted in enhanced CD8-dependent reduction of parasite load. However, continued overexpression of MHC I beyond 30 d ultimately led to a collapse of systemic parasite control associated with immune exhaustion, which was reversible in part by blocking PD-1:PD-L1 interactions. These studies demonstrate a surprisingly strong and systemically dominant effect of skeletal muscle MHC expression on maintaining T cell function and pathogen control and argue that the normally low MHC I expression in skeletal muscle is host protective by allowing for pathogen control while preventing immune exhaustion.

中文翻译：

---

前沿：增强肌肉 MHC 表达以 T 细胞耗竭为代价增强系统病原体控制

关键点 MHC I 可以以强力霉素剂量依赖性方式在骨骼肌中诱导。升高的肌肉 MHC I 导致对克氏锥虫的初始免疫控制增强。肌肉 MHC I 的持续升高最终会耗尽病原体特异性反应。肌细胞表达低水平的 MHC I 类 (MHC I)，这可能会影响 CD8+ T 细胞有效检测和破坏侵入肌肉的病原体的能力。克氏锥虫感染许多细胞类型，但优先存在于肌肉中，我们询问这种依赖于组织的持续性是否与 MHC 表达有关。在 T. cruzi 感染的前 20 天，小鼠骨骼肌 MHC I 的诱导性增强导致寄生虫负荷的 CD8 依赖性降低。然而，MHC I 的持续过表达超过 30 天最终导致与免疫衰竭相关的全身寄生虫控制崩溃，这部分是通过阻断 PD-1:PD-L1 相互作用来逆转的。这些研究证明骨骼肌 MHC 表达对维持 T 细胞功能和病原体控制具有惊人的强大和系统性显性影响，并认为骨骼肌中正常低的 MHC I 表达通过允许病原体控制同时防止免疫衰竭来保护宿主。