tetano
Editor, Senior Moderator
Nature
. 2021 Jan 11.
doi: 10.1038/s41586-020-03148-w. Online ahead of print.
Circuits between infected macrophages and T cells in SARS-CoV-2 pneumonia
Rogan A Grant[SUP] 1 [/SUP], Luisa Morales-Nebreda[SUP] 1 [/SUP], Nikolay S Markov[SUP] 1 [/SUP], Suchitra Swaminathan[SUP] 2 3 [/SUP], Melissa Querrey[SUP] 4 [/SUP], Estefany R Guzman[SUP] 3 [/SUP], Darryl A Abbott[SUP] 3 [/SUP], Helen K Donnelly[SUP] 1 [/SUP], Alvaro Donayre[SUP] 1 [/SUP], Isaac A Goldberg[SUP] 1 [/SUP], Zasu M Klug[SUP] 1 [/SUP], Nicole Borkowski[SUP] 1 [/SUP], Ziyan Lu[SUP] 1 [/SUP], Hermon Kihshen[SUP] 1 [/SUP], Yuliya Politanska[SUP] 1 [/SUP], Lango Sichizya[SUP] 1 [/SUP], Mengjia Kang[SUP] 1 [/SUP], Ali Shilatifard[SUP] 5 6 [/SUP], Chao Qi[SUP] 7 [/SUP], Jon W Lomasney[SUP] 7 [/SUP], A Christine Argento[SUP] 1 [/SUP], Jacqueline M Kruser[SUP] 1 [/SUP], Elizabeth S Malsin[SUP] 1 [/SUP], Chiagozie O Pickens[SUP] 1 [/SUP], Sean B Smith[SUP] 1 [/SUP], James M Walter[SUP] 1 [/SUP], Anna E Pawlowski[SUP] 8 [/SUP], Daniel Schneider[SUP] 8 [/SUP], Prasanth Nannapaneni[SUP] 8 [/SUP], Hiam Abdala-Valencia[SUP] 1 [/SUP], Ankit Bharat[SUP] 1 4 [/SUP], Cara J Gottardi[SUP] 1 [/SUP], G R Scott Budinger[SUP] 9 [/SUP], Alexander V Misharin[SUP] 10 11 [/SUP], Benjamin D Singer[SUP] 12 13 14 [/SUP], Richard G Wunderink[SUP] 15 16 [/SUP], NU SCRIPT Study Investigators
Collaborators, Affiliations
Abstract
Some patients infected with Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) develop severe pneumonia and the acute respiratory distress syndrome (ARDS)[SUP]1[/SUP]. 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 other types of pneumonia[SUP]2[/SUP]. 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 subjected them to flow cytometry and bulk transcriptomic profiling. We performed single-cell RNA-seq on 10 bronchoalveolar lavage fluid samples collected from patients with severe COVID-19 within 48 hours 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-gamma 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 harboring SARS-CoV-2 and T cells form a positive feedback loop that drives persistent alveolar inflammation.
. 2021 Jan 11.
doi: 10.1038/s41586-020-03148-w. Online ahead of print.
Circuits between infected macrophages and T cells in SARS-CoV-2 pneumonia
Rogan A Grant[SUP] 1 [/SUP], Luisa Morales-Nebreda[SUP] 1 [/SUP], Nikolay S Markov[SUP] 1 [/SUP], Suchitra Swaminathan[SUP] 2 3 [/SUP], Melissa Querrey[SUP] 4 [/SUP], Estefany R Guzman[SUP] 3 [/SUP], Darryl A Abbott[SUP] 3 [/SUP], Helen K Donnelly[SUP] 1 [/SUP], Alvaro Donayre[SUP] 1 [/SUP], Isaac A Goldberg[SUP] 1 [/SUP], Zasu M Klug[SUP] 1 [/SUP], Nicole Borkowski[SUP] 1 [/SUP], Ziyan Lu[SUP] 1 [/SUP], Hermon Kihshen[SUP] 1 [/SUP], Yuliya Politanska[SUP] 1 [/SUP], Lango Sichizya[SUP] 1 [/SUP], Mengjia Kang[SUP] 1 [/SUP], Ali Shilatifard[SUP] 5 6 [/SUP], Chao Qi[SUP] 7 [/SUP], Jon W Lomasney[SUP] 7 [/SUP], A Christine Argento[SUP] 1 [/SUP], Jacqueline M Kruser[SUP] 1 [/SUP], Elizabeth S Malsin[SUP] 1 [/SUP], Chiagozie O Pickens[SUP] 1 [/SUP], Sean B Smith[SUP] 1 [/SUP], James M Walter[SUP] 1 [/SUP], Anna E Pawlowski[SUP] 8 [/SUP], Daniel Schneider[SUP] 8 [/SUP], Prasanth Nannapaneni[SUP] 8 [/SUP], Hiam Abdala-Valencia[SUP] 1 [/SUP], Ankit Bharat[SUP] 1 4 [/SUP], Cara J Gottardi[SUP] 1 [/SUP], G R Scott Budinger[SUP] 9 [/SUP], Alexander V Misharin[SUP] 10 11 [/SUP], Benjamin D Singer[SUP] 12 13 14 [/SUP], Richard G Wunderink[SUP] 15 16 [/SUP], NU SCRIPT Study Investigators
Collaborators, Affiliations
- PMID: 33429418
- DOI: 10.1038/s41586-020-03148-w
Abstract
Some patients infected with Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) develop severe pneumonia and the acute respiratory distress syndrome (ARDS)[SUP]1[/SUP]. 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 other types of pneumonia[SUP]2[/SUP]. 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 subjected them to flow cytometry and bulk transcriptomic profiling. We performed single-cell RNA-seq on 10 bronchoalveolar lavage fluid samples collected from patients with severe COVID-19 within 48 hours 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-gamma 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 harboring SARS-CoV-2 and T cells form a positive feedback loop that drives persistent alveolar inflammation.