Macrophage S1PR2 Drives Sepsis-induced Immunosuppression by Exacerbating Mitochondrial Fragmentation

作者：Xiangyang Yu, Xin Hu, Dongdong Wang, Ping Cui, M. Zeng, Min Li, Chenchen Gong, Dongqin Huang, Yan Wang, Kai Zhang, Xiangming Fang · 发表于：American Journal of Respiratory Cell and Molecular Biology · 年份：2024 · DOI：10.1165/rcmb.2024-0161oc · 被引用次数：8 · 研究领域：Pneumocystis jirovecii pneumonia detection and treatment、interferon and immune responses、Amoebic Infections and Treatments

Abstract Macrophage mitochondrial dysfunction is associated with immunosuppression and poor prognosis of patients with sepsis. Mitochondrial fragmentation drives mitochondrial dysfunction. Our previous study has found that S1PR2 (sphingosine-1-phosphate receptor 2) regulates macrophage phagocytosis during sepsis, whereas the role of S1PR2 in immunosuppression and the mechanisms require further study. This study aimed to unveil the relationship between macrophage mitochondrial fragmentation and sepsis-induced immunosuppression, as well as the S1PR2-related mechanisms thereof. Peripheral blood monocytes were collected from healthy control subjects (n = 12), nonseptic critical control subjects (n = 13), and patients with sepsis (n = 19). Peritoneal macrophages were harvested from wild-type and S1pr2−/− mice (Mutant Mouse Regional Resource Centers strain ID, 12830) after cecal ligation and puncture (CLP). Mitochondrial ultrastructure was evaluated using transmission electron microscopy. The impact of mitochondrial ultrastructure alteration on immunosuppression of monocyte-macrophages was evaluated. Compared with nonseptic and healthy control subjects, peripheral blood monocytes from patients with sepsis exhibited increased S1PR2 expression, mitochondrial fragmentation, and mitochondrial dysfunction. Mitochondrial fragmentation was negatively associated with HLA-DR (human leukocyte antigen–DR isotype) expression. S1PR2 expression was positively correlated with mitochondrial fragme...