Circuits between infected macrophages and T cells in SARS-CoV-2 pneumonia
Some patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop severe pneumonia and acute respiratory distress syndrome1 (ARDS). Distinct clinical features in these patients have led to speculation that the immune response to virus in the SARS-CoV-2-infected alveolus differs from that in other types of pneumonia2. Here we investigate SARS-CoV-2 pathobiology by characterizing the immune response in the alveoli of patients infected with the virus. We collected bronchoalveolar lavage fluid samples from 88 patients with SARS-CoV-2-induced respiratory failure and 211 patients with known or suspected pneumonia from other pathogens, and analysed them using flow cytometry and bulk transcriptomic profiling. We performed single-cell RNA sequencing on 10 bronchoalveolar lavage fluid samples collected from patients with severe coronavirus disease 2019 (COVID-19) within 48 h of intubation. In the majority of patients with SARS-CoV-2 infection, the alveolar space was persistently enriched in T cells and monocytes. Bulk and single-cell transcriptomic profiling suggested that SARS-CoV-2 infects alveolar macrophages, which in turn respond by producing T cell chemoattractants. These T cells produce interferon-γ to induce inflammatory cytokine release from alveolar macrophages and further promote T cell activation. Collectively, our results suggest that SARS-CoV-2 causes a slowly unfolding, spatially limited alveolitis in which alveolar macrophages containing SARS-CoV-2 and T cells form a positive feedback loop that drives persistent alveolar inflammation.
Errataetall: |
CommentIn: Nature. 2021 Feb;590(7847):553-554. - PMID 33558748 |
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Medienart: |
E-Artikel |
Erscheinungsjahr: |
2021 |
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Erschienen: |
2021 |
Enthalten in: |
Zur Gesamtaufnahme - volume:590 |
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Enthalten in: |
Nature - 590(2021), 7847 vom: 19. Feb., Seite 635-641 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Grant, Rogan A [VerfasserIn] |
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Links: |
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Themen: |
82115-62-6 |
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Anmerkungen: |
Date Completed 02.03.2021 Date Revised 27.01.2023 published: Print-Electronic CommentIn: Nature. 2021 Feb;590(7847):553-554. - PMID 33558748 Citation Status MEDLINE |
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doi: |
10.1038/s41586-020-03148-w |
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funding: |
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PPN (Katalog-ID): |
NLM319928721 |
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500 | |a Citation Status MEDLINE | ||
520 | |a Some patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop severe pneumonia and acute respiratory distress syndrome1 (ARDS). Distinct clinical features in these patients have led to speculation that the immune response to virus in the SARS-CoV-2-infected alveolus differs from that in other types of pneumonia2. Here we investigate SARS-CoV-2 pathobiology by characterizing the immune response in the alveoli of patients infected with the virus. We collected bronchoalveolar lavage fluid samples from 88 patients with SARS-CoV-2-induced respiratory failure and 211 patients with known or suspected pneumonia from other pathogens, and analysed them using flow cytometry and bulk transcriptomic profiling. We performed single-cell RNA sequencing on 10 bronchoalveolar lavage fluid samples collected from patients with severe coronavirus disease 2019 (COVID-19) within 48 h of intubation. In the majority of patients with SARS-CoV-2 infection, the alveolar space was persistently enriched in T cells and monocytes. Bulk and single-cell transcriptomic profiling suggested that SARS-CoV-2 infects alveolar macrophages, which in turn respond by producing T cell chemoattractants. These T cells produce interferon-γ to induce inflammatory cytokine release from alveolar macrophages and further promote T cell activation. Collectively, our results suggest that SARS-CoV-2 causes a slowly unfolding, spatially limited alveolitis in which alveolar macrophages containing SARS-CoV-2 and T cells form a positive feedback loop that drives persistent alveolar inflammation | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, N.I.H., Extramural | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
650 | 4 | |a Research Support, U.S. Gov't, Non-P.H.S. | |
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700 | 1 | |a Goldberg, Isaac A |e investigator |4 oth | |
700 | 1 | |a Klug, Zasu M |e investigator |4 oth | |
700 | 1 | |a Borkowski, Nicole |e investigator |4 oth | |
700 | 1 | |a Lu, Ziyan |e investigator |4 oth | |
700 | 1 | |a Kihshen, Hermon |e investigator |4 oth | |
700 | 1 | |a Politanska, Yuliya |e investigator |4 oth | |
700 | 1 | |a Sichizya, Lango |e investigator |4 oth | |
700 | 1 | |a Kang, Mengjia |e investigator |4 oth | |
700 | 1 | |a Shilatifard, Ali |e investigator |4 oth | |
700 | 1 | |a Qi, Chao |e investigator |4 oth | |
700 | 1 | |a Lomasney, Jon W |e investigator |4 oth | |
700 | 1 | |a Argento, A Christine |e investigator |4 oth | |
700 | 1 | |a Kruser, Jacqueline M |e investigator |4 oth | |
700 | 1 | |a Malsin, Elizabeth S |e investigator |4 oth | |
700 | 1 | |a Pickens, Chiagozie O |e investigator |4 oth | |
700 | 1 | |a Smith, Sean B |e investigator |4 oth | |
700 | 1 | |a Walter, James M |e investigator |4 oth | |
700 | 1 | |a Pawlowski, Anna E |e investigator |4 oth | |
700 | 1 | |a Schneider, Daniel |e investigator |4 oth | |
700 | 1 | |a Nannapaneni, Prasanth |e investigator |4 oth | |
700 | 1 | |a Abdala-Valencia, Hiam |e investigator |4 oth | |
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700 | 1 | |a Wunderink, Richard G |e investigator |4 oth | |
700 | 1 | |a Wagh, Ajay A |e investigator |4 oth | |
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