Lipopolysaccharide and Glycolipoprotein Coordinately Triggered Necroptosis Contributes to the Pathogenesis of Leptospira Infection in Mice
Lipopolysaccharide and Glycolipoprotein Coordinately Triggered Necroptosis Contributes to the Pathogenesis of Leptospira Infection in Mice
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DOI：
10.1093/infdis/jiad151
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发表时间：
2023-05-11
影响因子：
6.4
通讯作者：
He，Ping
中科院分区：
文献类型：
--
作者：
Du，Lin;Wu，Yunqiang;He，Ping
Leptospirosis is a recurring but neglected zoonotic disease caused by pathogenicLeptospira. The explicit underlying mechanism of necroptosis and its role inLeptospirainfection have not yet been elucidated. Here we reported that leptospiral pathogen-associated molecular patterns, lipopolysaccharide, and glycolipoprotein activate the necroptotic RIPK1-RIPK3-MLKL cascade through the TLR4 signaling pathway in mouse macrophages. Using the murine acute leptospirosis model, we reveal that abolition of necroptosis exhibited significantly improved outcomes in acute phases, with enhanced eradication ofLeptospirafrom liver, mild clinical symptoms, and decreased cytokine production. RIPK3 was also found to exert a necroptosis-independent function in CXCL1 production and neutrophil recruitment, with the consequence of improvedLeptospiracontrol. These findings improve our understanding of the mechanism ofLeptospira-macrophage interactions, indicating potential therapeutic values by targeting necroptosis signaling pathways.
