生物
造血
骨髓生成
Toll样受体
免疫系统
某种肠道细菌
先天免疫系统
细胞生物学
TLR2型
祖细胞
髓样
免疫学
干细胞
肠道菌群
作者
Yuxin Wang,Tatsuya Morishima,Maiko Sezaki,Ryo Sato,Gaku Nakato,Shinji Fukuda,Kouji Kobiyama,Ken J. Ishii,Yuhua Li,Hajime Takizawa
标识
DOI:10.15252/embr.202357485
摘要
Abstract Bacterial infections can activate and mobilize hematopoietic stem and progenitor cells (HSPCs) from the bone marrow (BM) to the spleen, a process termed extramedullary hematopoiesis (EMH). Recent studies suggest that commensal bacteria regulate not only the host immune system but also hematopoietic homeostasis. However, the impact of gut microbes on hematopoietic pathology remains unclear. Here, we find that systemic single injections of Akkermansia muciniphila ( A. m .), a mucin‐degrading bacterium, rapidly activate BM myelopoiesis and slow but long‐lasting hepato‐splenomegaly, characterized by the expansion and differentiation of functional HSPCs, which we term delayed EMH. Mechanistically, delayed EMH triggered by A. m . is mediated entirely by the MYD88/TRIF innate immune signaling pathway, which persistently stimulates splenic myeloid cells to secrete interleukin (IL)‐1α, and in turn, activates IL‐1 receptor (IL‐1R)‐expressing splenic HSPCs. Genetic deletion of Toll‐like receptor‐2 and ‐4 (TLR2/4) or IL‐1α partially diminishes A. m .‐induced delayed EMH, while inhibition of both pathways alleviates splenomegaly and EMH. Our results demonstrate that cooperative IL‐1R‐ and TLR‐mediated signals regulate commensal bacteria‐driven EMH, which might be relevant for certain autoimmune disorders.
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