Host-derived oxidized phospholipids initiate effector-triggered immunity fostering lethality upon microbial encounter.
Host-derived oxidized phospholipids initiate effector-triggered immunity fostering lethality upon microbial encounter.
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宿主来源的氧化磷脂启动效应子触发的免疫，在微生物遭遇时产生致命性。
DOI：
10.1101/2023.11.21.568047
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Zanoni,Ivan
中科院分区：
文献类型：
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作者：
Gioia,MarcoDi;Poli,Valentina;Tan,PiaoJ;Spreafico,Roberto;Chu,Anne;Cuenca,AlexG;Gordts,PhilipLsm;Pandolfi,Laura;Meloni,Federica;Witztum,JosephL;Chou,Janet;Springstead,JamesR;Zanoni,Ivan
Macrophages detect invading microorganisms via pattern recognition receptors that recognize pathogen-associated molecular patterns, or via sensing the activity of virulence factors that initiates effector-triggered immunity (ETI). Tissue damage that follows pathogen encounter leads to the release of host-derived factors that participate to inflammation. How these self-derived molecules are sensed by macrophages and their impact on immunity remain poorly understood. Here we demonstrate that, in mice and humans, host-derived oxidized phospholipids (oxPLs) are formed upon microbial encounter. oxPL blockade restricts inflammation and prevents the death of the host, without affecting pathogen burden. Mechanistically, oxPLs bind and inhibit AKT, a master regulator of immunity and metabolism. AKT inhibition potentiates the methionine cycle, and epigenetically dampens Il10, a pluripotent anti-inflammatory cytokine. Overall, we found that host-derived inflammatory cues act as “self” virulence factors that initiate ETI and that their activity can be targeted to protect the host against excessive inflammation upon microbial encounter.
