Circuits between infected macrophages and T cells in SARS-CoV-2 pneumonia

Rogan A. Grant, Luisa Morales-Nebreda, Nikolay S. Markov, Suchitra Swaminathan, Melissa Querrey, Estefany R. Guzman, Darryl A. Abbott, Helen K. Donnelly, Alvaro Donayre, Isaac A. Goldberg, Zasu M. Klug, Nicole Borkowski, Ziyan Lu, Hermon Kihshen, Yuliya Politanska, Lango Sichizya, Mengjia Kang, Ali Shilatifard, Chao Qi, Jon W. Lomasney, A. Christine Argento, Jacqueline M. Kruser, Elizabeth S. Malsin, Chiagozie O. Pickens, Sean B. Smith, James M. Walter, Anna E. Pawlowski, Daniel Schneider, Prasanth Nannapaneni, Hiam Abdala-Valencia, Ankit Bharat, Cara J. Gottardi, G. R. Scott Budinger (), Alexander V. Misharin (), Benjamin D. Singer () and Richard G. Wunderink ()
Additional contact information
Rogan A. Grant: Northwestern University
Luisa Morales-Nebreda: Northwestern University
Nikolay S. Markov: Northwestern University
Suchitra Swaminathan: Northwestern University
Melissa Querrey: Northwestern University
Estefany R. Guzman: Northwestern University
Darryl A. Abbott: Northwestern University
Helen K. Donnelly: Northwestern University
Alvaro Donayre: Northwestern University
Isaac A. Goldberg: Northwestern University
Zasu M. Klug: Northwestern University
Nicole Borkowski: Northwestern University
Ziyan Lu: Northwestern University
Hermon Kihshen: Northwestern University
Yuliya Politanska: Northwestern University
Lango Sichizya: Northwestern University
Mengjia Kang: Northwestern University
Ali Shilatifard: Northwestern University
Chao Qi: Northwestern University
Jon W. Lomasney: Northwestern University
A. Christine Argento: Northwestern University
Jacqueline M. Kruser: Northwestern University
Elizabeth S. Malsin: Northwestern University
Chiagozie O. Pickens: Northwestern University
Sean B. Smith: Northwestern University
James M. Walter: Northwestern University
Anna E. Pawlowski: Northwestern University
Daniel Schneider: Northwestern University
Prasanth Nannapaneni: Northwestern University
Hiam Abdala-Valencia: Northwestern University
Ankit Bharat: Northwestern University
Cara J. Gottardi: Northwestern University
G. R. Scott Budinger: Northwestern University
Alexander V. Misharin: Northwestern University
Benjamin D. Singer: Northwestern University
Richard G. Wunderink: Northwestern University

Nature, 2021, vol. 590, issue 7847, 635-641

Abstract: Abstract 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.

Date: 2021
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DOI: 10.1038/s41586-020-03148-w

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