TLR9型
先天免疫系统
细胞因子
生物
免疫系统
败血症
免疫学
Toll样受体9
细胞激素风暴
细胞生物学
炎症
疾病
医学
基因
DNA甲基化
基因表达
生物化学
病理
传染病(医学专业)
2019年冠状病毒病(COVID-19)
作者
Lian Lam,S. Murphy,Dimitra Kokkinaki,Alessandro Venosa,Scott Sherrill-Mix,Carla Casu,Stefano Rivella,Aaron I. Weiner,Jeongho Park,Sunny Shin,Andrew E. Vaughan,Beatrice H. Hahn,Audrey Odom John,Nuala J. Meyer,Christopher A. Hunter,G. Scott Worthen,Nilam S. Mangalmurti
出处
期刊:Science Translational Medicine
[American Association for the Advancement of Science (AAAS)]
日期:2021-10-20
卷期号:13 (616)
被引量:94
标识
DOI:10.1126/scitranslmed.abj1008
摘要
Red blood cells (RBCs) are essential for aerobic respiration through delivery of oxygen to distant tissues. However, RBCs are currently considered immunologically inert, and few, if any, secondary functions of RBCs have been identified. Here, we showed that RBCs serve as critical immune sensors through surface expression of the nucleic acid–sensing Toll-like receptor 9 (TLR9). Mammalian RBCs expressed TLR9 on their surface and bound CpG-containing DNA derived from bacteria, plasmodia, and mitochondria. RBC-bound mitochondrial DNA was increased during human and murine sepsis and pneumonia. In vivo, CpG-carrying RBCs drove accelerated erythrophagocytosis and innate immune activation characterized by increased interferon signaling. Erythroid-specific deletion of TLR9 abrogated erythrophagocytosis and decreased local and systemic cytokine production during CpG-induced inflammation and polymicrobial sepsis. Thus, detection and capture of nucleic acid by TLR9-expressing RBCs regulated red cell clearance and inflammatory cytokine production, demonstrating that RBCs function as immune sentinels during pathologic states. Consistent with these findings, RBC-bound mitochondrial DNA was elevated in individuals with viral pneumonia and sepsis secondary to coronavirus disease 2019 (COVID-19) and associated with anemia and severity of disease. These findings uncover a previously unappreciated role of RBCs as critical players in inflammation distinct from their function in gas transport.
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