Immediate myeloid depot for SARS-CoV-2 in the human lung-Reference-Cited by-同舟云学术

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

Published:2024-08-02 Issue:31 Volume:10 Page:
ISSN:2375-2548
Container-title:Science Advances
language:en
Short-container-title:Sci. Adv.

Author:

Magnen Mélia¹^ORCID,You Ran²,Rao Arjun A.²³^ORCID,Davis Ryan T.²,Rodriguez Lauren³⁴^ORCID,Bernard Olivier¹^ORCID,Simoneau Camille R.¹⁵^ORCID,Hysenaj Lisiena⁶^ORCID,Hu Kenneth H.²^ORCID,Maishan Mazharul¹^ORCID,Conrad Catharina¹^ORCID,Gbenedio Oghenekevwe M.⁶^ORCID,Samad Bushra³^ORCID,Consortium The UCSF COMET⁷,Love Christina¹⁸,Woodruff Prescott G.¹^ORCID,Erle David J.¹^ORCID,Hendrickson Carolyn M.¹^ORCID,Calfee Carolyn S.¹,Matthay Michael A.¹^ORCID,Roose Jeroen P.⁶^ORCID,Sil Anita⁴⁸^ORCID,Ott Melanie¹⁵⁸^ORCID,Langelier Charles R.¹⁸^ORCID,Krummel Matthew F.²^ORCID,Looney Mark R.¹^ORCID

Affiliation:

1. Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.

2. Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA.

3. CoLabs Initiative, University of California, San Francisco, San Francisco, CA 94143, USA.

4. Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA.

5. Gladstone Institutes, San Francisco, CA 94158, USA.

6. Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA.

7. All UCSF COMET Consortium collaborators are affiliated with the University of California, San Francisco, San Francisco, CA 94143, USA.

8. Chan Zuckerberg Biohub, San Francisco, CA 94158, USA.

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.

Publisher

American Association for the Advancement of Science (AAAS)

Link

https://www.science.org/doi/pdf/10.1126/sciadv.adm8836

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