Whether autophagy affects methicillin-resistant Staphylococcus aureus (MRSA)-induced sepsis and the associated mechanisms are largely unknown. This study investigated the role of autophagy in MRSA-induced sepsis. The levels of microtubule-associated protein light chain 3 (LC3)-II/I, Beclin-1 and p62 after USA300 infection were examined by Western blotting and immunohistochemical staining. Bacterial burden analysis, hematoxylin-eosin staining, and Kaplan–Meier analysis were performed to evaluate the effect of autophagy on MRSA-induced sepsis. IFN-γ and IL-17 were analyzed by ELISA, and CD4⁺ T cell differentiation was assessed by flow cytometry. Our results showed that LC3-II/I and Beclin-1 were increased, while p62 was decreased after infection. Survival rates were decreased in the LC3B^−/− and Beclin-1^+/− groups, accompanied by worsened organ injuries and increased IFN-γ and IL-17 levels, whereas rapamycin alleviated organ damage, decreased IFN-γ and IL-17 levels, and improved the survival rate. However, there was no significant difference in bacterial burden. Flow cytometric analysis showed that rapamycin treatment decreased the frequencies of Th1 and Th17 cells, whereas these cells were upregulated in the LC3B^−/− and Beclin-1^+/− groups. Therefore, autophagy plays a protective role in MRSA-induced sepsis, which may be partly associated with the alleviation of organ injuries via the downregulation of Th1 and Th17 responses. These results provide a nonantibiotic treatment strategy for sepsis.

自噬是否会影响耐甲氧西林金黄色葡萄球菌(MRSA) 诱导的败血症以及相关机制在很大程度上是未知的。本研究调查了自噬在 MRSA 诱导的脓毒症中的作用。通过Western印迹和免疫组织化学染色检测USA300感染后微管相关蛋白轻链3（LC3）-II/I、Beclin-1和p62的水平。进行细菌负荷分析、苏木精-伊红染色和 Kaplan-Meier 分析以评估自噬对 MRSA 诱导的脓毒症的影响。用 ELISA 分析 IFN-γ 和 IL-17，CD4 ⁺通过流式细胞术评估 T 细胞分化。我们的结果表明感染后 LC3-II/I 和 Beclin-1 增加，而 p62 减少。^{LC3B -/-}和 Beclin-1 ^+/-组的存活率下降，伴随器官损伤恶化和 IFN-γ 和 IL-17 水平升高，而雷帕霉素减轻器官损伤，降低 IFN-γ 和 IL-17 水平，提高了成活率。然而，细菌负荷没有显着差异。流式细胞仪分析显示，雷帕霉素处理降低了 Th1 和 Th17 细胞的频率，而这些细胞在 LC3B ^-/-和 Beclin-1 ^+/-中上调团体。因此，自噬在 MRSA 诱导的脓毒症中起保护作用，这可能与通过下调 Th1 和 Th17 反应减轻器官损伤有关。这些结果为败血症提供了一种非抗生素治疗策略。