Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 41346 Gothenburg, Sweden.
Center for Clinical Laboratories, The Affiliated Hospital of Guizhou Medical University, Guiyang 550001, China.
Int J Mol Sci. 2021 Jul 1;22(13):7099. doi: 10.3390/ijms22137099.
(), a Gram-positive bacteria, is known to cause various infections. Extracellular vesicles (EVs) are a heterogeneous array of membranous structures secreted by cells from all three domains of life, i.e., eukaryotes, bacteria, and archaea. Bacterial EVs are implied to be involved in both bacteria-bacteria and bacteria-host interactions during infections. It is still unclear how EVs interact with host cells and induce inflammatory responses. In this study, EVs were isolated from and mutant strains deficient in either prelipoprotein lipidation (Δ) or major surface proteins (Δ). Their immunostimulatory capacities were assessed both in vitro and in vivo. We found that EVs induced pro-inflammatory responses both in vitro and in vivo. However, this activity was dependent on lipidated lipoproteins (Lpp), since EVs isolated from the Δ showed no stimulation. On the other hand, EVs isolated from the Δ mutant showed full immune stimulation, indicating the cell wall anchoring of surface proteins did not play a role in immune stimulation. The immune stimulation of EVs was mediated mainly by monocytes/macrophages and was TLR2 dependent. In this study, we demonstrated that not only free Lpp but also EV-imbedded Lpp had high pro-inflammatory activity.
（），一种革兰氏阳性细菌，已知可引起各种感染。细胞外囊泡 (EVs) 是一种由所有三个生命领域（真核生物、细菌和古菌）的细胞分泌的异质膜结构。细菌 EVs 被认为在感染期间参与细菌-细菌和细菌-宿主相互作用。目前尚不清楚 EVs 如何与宿主细胞相互作用并诱导炎症反应。在这项研究中，从 和缺失前脂蛋白脂质化（Δ）或主要表面蛋白（Δ）的突变株中分离 EVs。评估了它们在体外和体内的免疫刺激能力。我们发现 EVs 可在体外和体内诱导促炎反应。然而，这种活性依赖于脂化脂蛋白（Lpp），因为从 Δ 中分离的 EVs 没有刺激作用。另一方面，从 Δ 突变株中分离的 EVs 显示出完全的免疫刺激作用，表明表面蛋白的细胞壁锚定在免疫刺激中不起作用。EVs 的免疫刺激主要由单核细胞/巨噬细胞介导，并且依赖 TLR2。在这项研究中，我们证明了不仅游离的 Lpp，而且 EV 嵌入的 Lpp 都具有很高的促炎活性。
