Resolution of SARS-CoV-2 infection in human lung tissues is driven by extravascular CD163+ monocytes
The lung-resident immune mechanisms driving resolution of SARS-CoV-2 infection in humans remain elusive. Using mice co-engrafted with a genetically matched human immune system and fetal lung xenograft (fLX), we mapped the immunological events defining resolution of SARS-CoV-2 infection in human lung tissues. Viral infection is rapidly cleared from fLX following a peak of viral replication. Acute replication results in the emergence of cell subsets enriched in viral RNA, including extravascular inflammatory monocytes (iMO) and macrophage-like T-cells, which dissipate upon infection resolution. iMO display robust antiviral responses, are transcriptomically unique among myeloid lineages, and their emergence associates with the recruitment of circulating CD4+ monocytes. Consistently, mice depleted for human CD4+ cells but not CD3+ T-cells failed to robustly clear infectious viruses and displayed signatures of chronic infection. Our findings uncover the transient differentiation of extravascular iMO from CD4+ monocytes as a major hallmark of SARS-CoV-2 infection resolution and open avenues for unravelling viral and host adaptations defining persistently active SARS-CoV-2 infection.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
bioRxiv : the preprint server for biology - (2024) vom: 08. März |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kenney, Devin [VerfasserIn] |
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| Anmerkungen: |
Date Revised 21.03.2024 published: Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1101/2024.03.08.583965 |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM36986154X |
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| 245 | 1 | 0 | |a Resolution of SARS-CoV-2 infection in human lung tissues is driven by extravascular CD163+ monocytes |
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| 520 | |a The lung-resident immune mechanisms driving resolution of SARS-CoV-2 infection in humans remain elusive. Using mice co-engrafted with a genetically matched human immune system and fetal lung xenograft (fLX), we mapped the immunological events defining resolution of SARS-CoV-2 infection in human lung tissues. Viral infection is rapidly cleared from fLX following a peak of viral replication. Acute replication results in the emergence of cell subsets enriched in viral RNA, including extravascular inflammatory monocytes (iMO) and macrophage-like T-cells, which dissipate upon infection resolution. iMO display robust antiviral responses, are transcriptomically unique among myeloid lineages, and their emergence associates with the recruitment of circulating CD4+ monocytes. Consistently, mice depleted for human CD4+ cells but not CD3+ T-cells failed to robustly clear infectious viruses and displayed signatures of chronic infection. Our findings uncover the transient differentiation of extravascular iMO from CD4+ monocytes as a major hallmark of SARS-CoV-2 infection resolution and open avenues for unravelling viral and host adaptations defining persistently active SARS-CoV-2 infection | ||
| 650 | 4 | |a Preprint | |
| 700 | 1 | |a O'Connell, Aoife K |e verfasserin |4 aut | |
| 700 | 1 | |a Tseng, Anna E |e verfasserin |4 aut | |
| 700 | 1 | |a Turcinovic, Jacquelyn |e verfasserin |4 aut | |
| 700 | 1 | |a Sheehan, Meagan L |e verfasserin |4 aut | |
| 700 | 1 | |a Nitido, Adam D |e verfasserin |4 aut | |
| 700 | 1 | |a Montanaro, Paige |e verfasserin |4 aut | |
| 700 | 1 | |a Gertje, Hans P |e verfasserin |4 aut | |
| 700 | 1 | |a Ericsson, Maria |e verfasserin |4 aut | |
| 700 | 1 | |a Connor, John H |e verfasserin |4 aut | |
| 700 | 1 | |a Vrbanac, Vladimir |e verfasserin |4 aut | |
| 700 | 1 | |a Crossland, Nicholas A |e verfasserin |4 aut | |
| 700 | 1 | |a Harly, Christelle |e verfasserin |4 aut | |
| 700 | 1 | |a Balazs, Alejandro B |e verfasserin |4 aut | |
| 700 | 1 | |a Douam, Florian |e verfasserin |4 aut | |
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