Immediate myeloid depot for SARS-CoV-2 in the human lung

Sci Adv. 2024 Aug 2;10(31):eadm8836. doi: 10.1126/sciadv.adm8836. Epub 2024 Jul 31.

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.

MeSH terms

  • Angiotensin-Converting Enzyme 2* / metabolism
  • COVID-19* / immunology
  • COVID-19* / virology
  • Humans
  • Lung* / immunology
  • Lung* / pathology
  • Lung* / virology
  • Macrophages, Alveolar* / immunology
  • Macrophages, Alveolar* / metabolism
  • Macrophages, Alveolar* / virology
  • Myeloid Cells* / immunology
  • Myeloid Cells* / metabolism
  • Myeloid Cells* / virology
  • SARS-CoV-2* / physiology
  • Spike Glycoprotein, Coronavirus / immunology
  • Spike Glycoprotein, Coronavirus / metabolism
  • Viral Tropism
  • Virus Internalization

Substances

  • Angiotensin-Converting Enzyme 2
  • ACE2 protein, human
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2