Immediate myeloid depot for SARS-CoV-2 in the human lung
Mélia Magnen, Ran You, Arjun A. Rao, Ryan T. Davis, Lauren Rodriguez, O Bernard, Camille R. Simoneau, Lisiena Hysenaj, Kenneth H. Hu, Mazharul Maishan, Catharina Conrad, Oghenekevwe M. Gbenedio, Bushra Samad, Christina Love, Prescott G. Woodruff, David J. Erle, Carolyn M. Hendrickson, Carolyn S. Calfee, Michael A. Matthay, Jeroen P. Roose, Anita Sil, Mélanie Ott, Charles Langelier, Matthew F. Krummel, Mark R. Looney
Abstract
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.