Kimmel Center for Biology and Medicine at the Skirball Institute, New York University Grossman School of Medicine, New York, NY, USA.
Department of Microbiology, New York University Grossman School of Medicine, New York, NY, USA.
Autophagy. 2023 Jun;19(6):1887-1889. doi: 10.1080/15548627.2022.2146894. Epub 2022 Nov 21.
In recent years, the contribution of exosomes to immunity, inflammation and host-pathogen interaction have been appreciated. Exosomes are small secreted extracellular vesicles from endosomal origin that contain a myriad of cellular molecules (protein, nucleic acids), including surface receptors. We have reported a pathogen-induced and macroautophagy/autophagy-dependent class of exosomes coined as "defensosomes", which protect the host from membrane-targeting toxins. In a recent study, we found that defensosomes decorated with ACE2, the SARS-CoV-2 cellular receptor, are produced in the lungs of patients with COVID-19, and that increased concentration of ACE2-loaded defensosomes is associated with decreased hospitalization length. Mechanistically, SARS-CoV-2 induces the production of ACE2-coated defensosomes, a process requiring the autophagy machinery, which in turn binds and neutralizes the virus. We propose that defensosomes represent a new form of autophagy-mediated innate immunity that contributes to the host's armamentarium against pathogens.
近年来，人们越来越关注细胞外囊泡（exosomes）在免疫、炎症和宿主-病原体相互作用中的作用。细胞外囊泡是源自内体的小型分泌型细胞外囊泡，其中包含多种细胞分子（蛋白质、核酸），包括表面受体。我们曾报道过一种由病原体诱导并依赖巨自噬/自噬产生的一类细胞外囊泡，称为“防御体（defensosomes）”，它可以保护宿主免受膜靶向毒素的侵害。在最近的一项研究中，我们发现 COVID-19 患者肺部会产生带有 SARS-CoV-2 细胞受体 ACE2 的防御体，并且 ACE2 负载的防御体浓度增加与住院时间缩短有关。从机制上讲，SARS-CoV-2 诱导 ACE2 包被的防御体的产生，这一过程需要自噬机制，而自噬机制反过来又可以结合并中和病毒。我们提出，防御体代表了一种新的自噬介导体液免疫形式，有助于宿主对抗病原体的防御机制。
