美国康涅狄格大学健康中心Vijay A. Rathinam研究组在研究中取得进展。他们发现细菌脂多糖(LPS)利用宿主细胞外囊泡的非经典炎症小体感应和裂解作用进入细胞。2023年11月16日，国际学术期刊《自然-细胞生物学》发表了这一成果。

研究人员发现宿主来源的细胞外囊泡(EV)在这一过程中的作用。人和鼠血浆来源和细胞培养来源的EV具有结合LPS的内在能力。值得注意的是，循环系统中宿主EV在体内捕获血液中的LPS，而包含LPS的EV介导LPS进入细胞膜，从而引发非经典炎性体激活gasdermin D和热蛋白沉积。

从机制上讲，EVs的脂质双分子层与LPS脂质A之间的相互作用是EVs捕获LPS的基础，而CD14介导了EVs在细胞内转移LPS。总之，该研究表明，EVs可捕获并系统性递送LPS到细胞质，从而导致炎性反应，这表明EVs是之前未知的微生物配体与细胞内监控之间的联结因子。

据了解，在机体平衡和感染时，细胞对全身微生物组分的监控制约着宿主的生理和免疫。然而，一个长期存在的问题是细胞内受体如何识别循环系统中的微生物配体。

附：英文原文

Title: Host extracellular vesicles confer cytosolic access to systemic LPS licensing non-canonical inflammasome sensing and pyroptosis

Author: Kumari, Puja, Vasudevan, Swathy O., Russo, Ashley J., Wright, Skylar S., Fraile-greda, Vctor, Krajewski, Dylan, Jellison, Evan R., Rubio, Ignacio, Bauer, Michael, Shimoyama, Atsushi, Fukase, Koichi, Zhang, Yuanpeng, Pachter, Joel S., Vanaja, Sivapriya Kailasan, Rathinam, Vijay A.

Issue&Volume: 2023-11-16

Abstract: Intracellular surveillance for systemic microbial components during homeostasis and infections governs host physiology and immunity. However, a long-standing question is how circulating microbial ligands become accessible to intracellular receptors. Here we show a role for host-derived extracellular vesicles (EVs) in this process; human and murine plasma-derived and cell culture-derived EVs have an intrinsic capacity to bind bacterial lipopolysaccharide (LPS). Remarkably, circulating host EVs capture blood-borne LPS in vivo, and the LPS-laden EVs confer cytosolic access for LPS, triggering non-canonical inflammasome activation of gasdermin D and pyroptosis. Mechanistically, the interaction between the lipid bilayer of EVs and the lipid A of LPS underlies EV capture of LPS, and the intracellular transfer of LPS by EVs is mediated by CD14. Overall, this study demonstrates that EVs capture and escort systemic LPS to the cytosol licensing inflammasome responses, uncovering EVs as a previously unrecognized link between systemic microbial ligands and intracellular surveillance.

DOI: 10.1038/s41556-023-01269-8

Source: https://www.nature.com/articles/s41556-023-01269-8