Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg.
Department of Life Sciences and Medicine, Faculty of Science, Technology and Medicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg.
Front Immunol. 2020 Dec 21;11:583644. doi: 10.3389/fimmu.2020.583644. eCollection 2020.
Extracellular vesicles (EVs) derived from the gut microbiota are largely uncharacterized and their impacts on host intestinal physiology remain unresolved. Here, we isolated EVs from for detailed characterization. Our analyses highlight the presence of the outer membrane protein porin FomA on EVs. Besides, we evaluated the impact of EVs on human intestinal epithelial cells (IECs) in a non-inflammatory context. Our results show no detrimental impact on the epithelial barrier. No internalization of EVs was observed. Moreover, we demonstrate that EVs trigger innate immunity of IECs by promoting NF-κB activation the dynamin-mediated endocytosis. The NF-κB activation was found to be TLR2-dependent yet, TLR4 was dispensable. Using competitive binding assays, we establish that FomA is involved in the NF-κB response. Taken together, our data indicate that EVs induce effects similar to those observed with whole bacteria on IECs. In particular, our study highlights the role of TLR2 and FomA as major modulators of the gut epithelium immune responses to .
肠道微生物衍生的细胞外囊泡（EVs）在很大程度上尚未被阐明，其对宿主肠道生理学的影响仍未得到解决。在这里，我们从 中分离 EVs 进行详细表征。我们的分析强调了外膜蛋白 porin FomA 在 EVs 上的存在。此外，我们在非炎症情况下评估了 EVs 对人肠上皮细胞（IECs）的影响。我们的结果表明，EVs 不会对上皮屏障造成损害。没有观察到 EVs 的内化。此外，我们证明 EVs 通过促进 NF-κB 激活和细胞质分裂蛋白 21（ dynamin）介导的内吞作用来触发 IECs 的先天免疫。发现 NF-κB 激活依赖于 TLR2，但 TLR4 是可有可无的。通过竞争性结合测定，我们确定 FomA 参与 NF-κB 反应。总之，我们的数据表明 EVs 诱导的效应类似于用完整的 细菌在 IECs 上观察到的效应。特别是，我们的研究强调了 TLR2 和 FomA 作为肠道上皮细胞对 的免疫反应的主要调节剂的作用。
