Resolution of SARS-CoV-2 infection in human lung tissues is driven by extravascular CD163+ monocytes
ABSTRACT 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: |
Preprint |
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Erscheinungsjahr: |
2024 |
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Erschienen: |
2024 |
Enthalten in: |
bioRxiv.org - (2024) vom: 12. März Zur Gesamtaufnahme - year:2024 |
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Sprache: |
Englisch |
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Beteiligte Personen: |
Kenney, Devin [VerfasserIn] |
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Links: |
Volltext [kostenfrei] |
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Themen: |
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doi: |
10.1101/2024.03.08.583965 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
XBI042843367 |
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520 | |a ABSTRACT 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. | ||
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700 | 1 | |a O’Connell, Aoife K. |4 aut | |
700 | 1 | |a Tseng, Anna E. |4 aut | |
700 | 1 | |a Turcinovic, Jacquelyn |4 aut | |
700 | 1 | |a Sheehan, Meagan L. |4 aut | |
700 | 1 | |a Nitido, Adam D. |4 aut | |
700 | 1 | |a Montanaro, Paige |4 aut | |
700 | 1 | |a Gertje, Hans P. |4 aut | |
700 | 1 | |a Ericsson, Maria |4 aut | |
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