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Dorchester Road Library
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Interstitial macrophages are a focus of viral takeover and inflammation in COVID-19 initiation in human lung.
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- Author(s): Wu TT;Wu TT;Wu TT; Travaglini KJ; Travaglini KJ; Travaglini KJ; Rustagi A; Rustagi A; Xu D; Xu D; Xu D; Zhang Y; Zhang Y; Zhang Y; Zhang Y; Andronov L; Andronov L; Jang S; Jang S; Jang S; Gillich A; Gillich A; Gillich A; Dehghannasiri R; Dehghannasiri R; Dehghannasiri R; Martínez-Colón GJ; Martínez-Colón GJ; Martínez-Colón GJ; Beck A; Beck A; Liu DD; Liu DD; Wilk AJ; Wilk AJ; Wilk AJ; Morri M; Morri M; Trope WL; Trope WL; Bierman R; Bierman R; Weissman IL; Weissman IL; Weissman IL; Shrager JB; Shrager JB; Shrager JB; Quake SR; Quake SR; Quake SR; Kuo CS; Kuo CS; Salzman J; Salzman J; Salzman J; Moerner WE; Moerner WE; Kim PS; Kim PS; Kim PS; Kim PS; Blish CA; Blish CA; Blish CA; Blish CA; Krasnow MA; Krasnow MA; Krasnow MA; Krasnow MA
- Source:
The Journal of experimental medicine [J Exp Med] 2024 Jun 03; Vol. 221 (6). Date of Electronic Publication: 2024 Apr 10.- Publication Type:
Journal Article- Language:
English - Source:
- Additional Information
- Source: Publisher: Rockefeller University Press Country of Publication: United States NLM ID: 2985109R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1540-9538 (Electronic) Linking ISSN: 00221007 NLM ISO Abbreviation: J Exp Med Subsets: MEDLINE
- Publication Information: Original Publication: New York, NY : Rockefeller University Press
- Subject Terms:
- Abstract: Early stages of deadly respiratory diseases including COVID-19 are challenging to elucidate in humans. Here, we define cellular tropism and transcriptomic effects of SARS-CoV-2 virus by productively infecting healthy human lung tissue and using scRNA-seq to reconstruct the transcriptional program in "infection pseudotime" for individual lung cell types. SARS-CoV-2 predominantly infected activated interstitial macrophages (IMs), which can accumulate thousands of viral RNA molecules, taking over 60% of the cell transcriptome and forming dense viral RNA bodies while inducing host profibrotic (TGFB1, SPP1) and inflammatory (early interferon response, CCL2/7/8/13, CXCL10, and IL6/10) programs and destroying host cell architecture. Infected alveolar macrophages (AMs) showed none of these extreme responses. Spike-dependent viral entry into AMs used ACE2 and Sialoadhesin/CD169, whereas IM entry used DC-SIGN/CD209. These results identify activated IMs as a prominent site of viral takeover, the focus of inflammation and fibrosis, and suggest targeting CD209 to prevent early pathology in COVID-19 pneumonia. This approach can be generalized to any human lung infection and to evaluate therapeutics.
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- Accession Number: 0 (RNA, Viral)
- Publication Date: Date Created: 20240410 Date Completed: 20240411 Latest Revision: 20240425
- Publication Date: 20240425
- Accession Number: PMC11009983
- Accession Number: 10.1084/jem.20232192
- Accession Number: 38597954
- Source:
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