Immediate myeloid depot for SARS-CoV-2 in the human lung.
Melia MagnenRan YouArjun Arkal RaoRyan T DavisLauren RodriguezOlivier BernardCamille R SimoneauLisiena HysenajKenneth H HuMazharul MaishanCatharina ConradOghenekevwe M GbenedioBushra SamadThe Ucsf Comet ConsortiumChristina LovePrescott G WoodruffDavid J ErleCarolyn M HendricksonCarolyn S CalfeeMichael A MatthayJeroen P RooseAnita SilMelanie M OttCharles R LangelierMatthew F KrummelMark R LooneyPublished in: Science advances (2024)
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.
Keyphrases
- sars cov
- respiratory syndrome coronavirus
- angiotensin converting enzyme
- endothelial cells
- angiotensin ii
- dendritic cells
- immune response
- induced pluripotent stem cells
- acute myeloid leukemia
- magnetic resonance
- pluripotent stem cells
- induced apoptosis
- coronavirus disease
- cell death
- sensitive detection
- inflammatory response