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Immediate myeloid depot for SARS-CoV-2 in the human lung.
Magnen, Mélia; You, Ran; Rao, Arjun A; Davis, Ryan T; Rodriguez, Lauren; Bernard, Olivier; Simoneau, Camille R; Hysenaj, Lisiena; Hu, Kenneth H; Maishan, Mazharul; Conrad, Catharina; Gbenedio, Oghenekevwe M; Samad, Bushra; Consortium, The Ucsf Comet; Love, Christina; Woodruff, Prescott G; Erle, David J; Hendrickson, Carolyn M; Calfee, Carolyn S; Matthay, Michael A; Roose, Jeroen P; Sil, Anita; Ott, Melanie; Langelier, Charles R; Krummel, Matthew F; Looney, Mark R.
Afiliação
  • Magnen M; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
  • You R; Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Rao AA; Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Davis RT; CoLabs Initiative, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Rodriguez L; Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Bernard O; CoLabs Initiative, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Simoneau CR; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Hysenaj L; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Hu KH; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Maishan M; Gladstone Institutes, San Francisco, CA 94158, USA.
  • Conrad C; Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Gbenedio OM; Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Samad B; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Consortium TUC; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Love C; Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Woodruff PG; CoLabs Initiative, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Erle DJ; All UCSF COMET Consortium collaborators are affiliated with the University of California, San Francisco, San Francisco, CA 94143, USA.
  • Hendrickson CM; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Calfee CS; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA.
  • Matthay MA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Roose JP; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Sil A; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Ott M; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Langelier CR; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Krummel MF; Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Looney MR; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA.
Sci Adv ; 10(31): eadm8836, 2024 Aug 02.
Article em En | MEDLINE | ID: mdl-39083602
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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Macrófagos Alveolares / Células Mieloides / Enzima de Conversão de Angiotensina 2 / SARS-CoV-2 / COVID-19 / Pulmão Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Macrófagos Alveolares / Células Mieloides / Enzima de Conversão de Angiotensina 2 / SARS-CoV-2 / COVID-19 / Pulmão Idioma: En Ano de publicação: 2024 Tipo de documento: Article