Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA.
Sci Adv. 2024 Aug 2;10(31):eadm8836. doi: 10.1126/sciadv.adm8836. Epub 2024 Jul 31.
In the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, epithelial populations in the distal lung expressing Angiotensin-converting enzyme 2 (ACE2) are infrequent, and therefore, the model of viral expansion and immune cell engagement remains incompletely understood. Using human lungs to investigate early host-viral pathogenesis, we found that SARS-CoV-2 had a rapid and specific tropism for myeloid populations. Human alveolar macrophages (AMs) reliably expressed ACE2 allowing both spike-ACE2-dependent viral entry and infection. In contrast to Influenza A virus, SARS-CoV-2 infection of AMs was productive, amplifying viral titers. While AMs generated new viruses, the interferon responses to SARS-CoV-2 were muted, hiding the viral dissemination from specific antiviral immune responses. The reliable and veiled viral depot in myeloid cells in the very early phases of SARS-CoV-2 infection of human lungs enables viral expansion in the distal lung and potentially licenses subsequent immune pathologies.
在严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）感染的发病机制中，远端肺部表达血管紧张素转换酶 2（ACE2）的上皮细胞群并不常见，因此，病毒扩增和免疫细胞参与的模型仍不完全清楚。我们使用人类肺来研究早期宿主-病毒发病机制，发现 SARS-CoV-2 对髓样细胞群具有快速和特异性的趋向性。人类肺泡巨噬细胞（AMs）可靠地表达 ACE2，允许刺突-ACE2 依赖性病毒进入和感染。与甲型流感病毒不同，SARS-CoV-2 感染 AMs 是有生产力的，可扩增病毒滴度。虽然 AMs 产生了新的病毒，但对 SARS-CoV-2 的干扰素反应被抑制，从而使特定的抗病毒免疫反应无法察觉病毒的传播。在 SARS-CoV-2 感染人类肺部的早期阶段，髓样细胞中可靠且隐蔽的病毒储存库使病毒在远端肺部中扩增，并可能允许随后发生免疫病理学。
Zotero 插件
