TY - JOUR
T1 - Circuits between infected macrophages and T cells in SARS-CoV-2 pneumonia
AU - The NU SCRIPT Study Investigators
AU - Morales-Nebreda, Luisa
AU - Borkowski, Nicole
AU - Qi, Chao
AU - Lomasney, Jon W.
AU - Argento, A. Christine
AU - Kruser, Jacqueline M.
AU - Malsin, Elizabeth S.
AU - Smith, Sean B.
AU - Walter, James M.
AU - Abdala-Valencia, Hiam
AU - Bharat, Ankit
AU - Gottardi, Cara J.
AU - Misharin, Alexander V.
AU - Singer, Benjamin D.
AU - Swaminathan, Suchitra
AU - Shilatifard, Ali
AU - Kruser, Jacqueline Marie
AU - Pickens, Chiagozie O.
AU - Wunderink, Richard G.
AU - Hauser, Alan R.
AU - Yeldandi, Anjana V.
AU - Tran, Betty
AU - Kurihara, Chitaru
AU - Schroedl, Clara J.
AU - Horvath, Curt M.
AU - Odell, David D.
AU - Kamp, David W.
AU - Winter, Deborah R.
AU - Ozer, Egon A.
AU - Shanes, Elisheva D.
AU - Bartom, Elizabeth T.
AU - Wehbe, Firas
AU - Sznajder, Jacob I.
AU - Dematte, Jane E.
AU - Coleman, John
AU - Fiala, Justin A.
AU - Starren, Justin
AU - Ridge, Karen M.
AU - Gates, Khalilah L.
AU - Wolfe, Lisa F.
AU - Pesce, Lorenzo L.
AU - Nunes Amaral, Luís A.
AU - Kandpal, Manoj
AU - Jain, Manu
AU - Sala, Marc A.
AU - Alexander, Michael J.
AU - Cuttica, Michael J.
AU - Prickett, Michelle H.
AU - Chandel, Navdeep S.
AU - Soulakis, Nicholas D.
AU - Seed, Patrick C.
AU - Reyfman, Paul A.
AU - Sporn, Peter H.S.
AU - Tomic, Rade
AU - Garza-Castillon, Rafael
AU - Kalhan, Ravi
AU - Morimoto, Richard I.
AU - Kim, Samuel S.
AU - Han, Seung Hye
AU - Rosenberg, Sharon R.
AU - Russell, Susan R.
N1 - Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2021/2/25
Y1 - 2021/2/25
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=85099648337&partnerID=8YFLogxK
U2 - 10.1038/s41586-020-03148-w
DO - 10.1038/s41586-020-03148-w
M3 - Article
C2 - 33429418
AN - SCOPUS:85099648337
SN - 0028-0836
VL - 590
SP - 635
EP - 641
JO - Nature
JF - Nature
IS - 7847
ER -