tetano
Editor, Senior Moderator
Sci Adv
. 2024 Aug 2;10(31):eadm8836.
doi: 10.1126/sciadv.adm8836. Epub 2024 Jul 31. Immediate myeloid depot for SARS-CoV-2 in the human lung
Mélia Magnen[SUP] 1 [/SUP], Ran You[SUP] 2 [/SUP], Arjun A Rao[SUP] 2 3 [/SUP], Ryan T Davis[SUP] 2 [/SUP], Lauren Rodriguez[SUP] 3 4 [/SUP], Olivier Bernard[SUP] 1 [/SUP], Camille R Simoneau[SUP] 1 5 [/SUP], Lisiena Hysenaj[SUP] 6 [/SUP], Kenneth H Hu[SUP] 2 [/SUP], Mazharul Maishan[SUP] 1 [/SUP], Catharina Conrad[SUP] 1 [/SUP], Oghenekevwe M Gbenedio[SUP] 6 [/SUP], Bushra Samad[SUP] 3 [/SUP], The Ucsf Comet Consortium[SUP] 7 [/SUP], Christina Love[SUP] 1 8 [/SUP], Prescott G Woodruff[SUP] 1 [/SUP], David J Erle[SUP] 1 [/SUP], Carolyn M Hendrickson[SUP] 1 [/SUP], Carolyn S Calfee[SUP] 1 [/SUP], Michael A Matthay[SUP] 1 [/SUP], Jeroen P Roose[SUP] 6 [/SUP], Anita Sil[SUP] 4 8 [/SUP], Melanie Ott[SUP] 1 5 8 [/SUP], Charles R Langelier[SUP] 1 8 [/SUP], Matthew F Krummel[SUP] 2 [/SUP], Mark R Looney[SUP] 1 [/SUP]
Affiliations
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.
. 2024 Aug 2;10(31):eadm8836.
doi: 10.1126/sciadv.adm8836. Epub 2024 Jul 31. Immediate myeloid depot for SARS-CoV-2 in the human lung
Mélia Magnen[SUP] 1 [/SUP], Ran You[SUP] 2 [/SUP], Arjun A Rao[SUP] 2 3 [/SUP], Ryan T Davis[SUP] 2 [/SUP], Lauren Rodriguez[SUP] 3 4 [/SUP], Olivier Bernard[SUP] 1 [/SUP], Camille R Simoneau[SUP] 1 5 [/SUP], Lisiena Hysenaj[SUP] 6 [/SUP], Kenneth H Hu[SUP] 2 [/SUP], Mazharul Maishan[SUP] 1 [/SUP], Catharina Conrad[SUP] 1 [/SUP], Oghenekevwe M Gbenedio[SUP] 6 [/SUP], Bushra Samad[SUP] 3 [/SUP], The Ucsf Comet Consortium[SUP] 7 [/SUP], Christina Love[SUP] 1 8 [/SUP], Prescott G Woodruff[SUP] 1 [/SUP], David J Erle[SUP] 1 [/SUP], Carolyn M Hendrickson[SUP] 1 [/SUP], Carolyn S Calfee[SUP] 1 [/SUP], Michael A Matthay[SUP] 1 [/SUP], Jeroen P Roose[SUP] 6 [/SUP], Anita Sil[SUP] 4 8 [/SUP], Melanie Ott[SUP] 1 5 8 [/SUP], Charles R Langelier[SUP] 1 8 [/SUP], Matthew F Krummel[SUP] 2 [/SUP], Mark R Looney[SUP] 1 [/SUP]
Affiliations
- PMID: 39083602
- PMCID: PMC11290487
- DOI: 10.1126/sciadv.adm8836
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.