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

2021; Nature Portfolio; Volume: 590; Issue: 7847 Linguagem: Inglês

10.1038/s41586-020-03148-w

1476-4687

Rogan A. Grant, Luisa Morales‐Nebreda, Nikolay S. Markov, Suchitra Swaminathan, Melissa Querrey, Estefany Rios-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 I. Pickens, Sean B. Smith, James M. Walter, Anna Pawlowski, Daniel Schneider, Prasanth Nannapaneni, Hiam Abdala‐Valencia, Ankit Bharat, Cara J. Gottardi, G. R. Scott Budinger, Alexander V. Misharin, Benjamin D. Singer, Richard G. Wunderink, Rogan A. Grant, Luisa Morales‐Nebreda, Nikolay S. Markov, Suchitra Swaminathan, Melissa Querrey, Estefany Rios-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 I. Pickens, Sean B. Smith, James M. Walter, Anna Pawlowski, Daniel Schneider, Prasanth Nannapaneni, Hiam Abdala‐Valencia, Ankit Bharat, Cara J. Gottardi, G. R. Scott Budinger, Alexander V. Misharin, Benjamin D. Singer, Richard G. Wunderink, Ajay A. Wagh, Alan R. Hauser, Alexis Rose Wolfe, Anjali Thakrar, Anjana V. Yeldandi, Ann A. Wang, Anne R. Levenson, Anthony M. Joudi, Betty T. Tran, Catherine A. Gao, Chitaru Kurihara, Clara Schroedl, Curt M. Horvath, Daniel Meza, David D. Odell, David W. Kamp, Deborah R. Winter, Egon A. Ozer, Elisheva D. Shanes, Elizabeth T. Bartom, Emily J. Rendleman, Emily M. Leibenguth, Firas Wehbe, Gabrielle Y. Liu, Gaurav Gadhvi, Heliodoro Tejedor Navarro, Jacob I. Sznajder, Jane E. Dematte, Jasmine Le, Jason Arnold, Joanne C. Du, John M. Coleman, Joseph I. Bailey, Joseph S. Deters, Justin A. Fiala, Justin Starren, Karen M. Ridge, Katharine Secunda, Kathleen Aren, Khalilah L. Gates, Kristy Todd, Lindsey D. Gradone, Lindsey N. Textor, Lisa F. Wolfe, Lorenzo L. Pesce, Luı́s A. Nunes Amaral, Madeline L. Rosenbaum, Manoj Kandpal, Manu Jain, Marc A. Sala, Mark Saine, Mary Carns, Michael Alexander, Michael J. Cuttica, Michelle Prickett, Nabiha Khan, Navdeep S. Chandel, Nicholas D. Soulakis, Orlyn Rivas, Patrick C. Seed, Paul A. Reyfman, Pearl D. Go, Peter H. S. Sporn, Phillip R. Cooper, Rade Tomic, Radhika A. Patel, Rafael Garza‐Castillon, Ravi Kalhan, Richard I. Morimoto, Ruben Mylvaganam, Samuel S. Kim, Samuel W. M. Gatesy, Sanket Thakkar, Sarah Ben Maamar, SeungHye Han, Sharon R Rosenberg, Sophia Nozick, Stefan J. Green, Susan Russell, Taylor A. Poor, Taylor Zak, Theresa A. Lombardo, Thomas Stoeger, Todd Shamaly, Ziyou Ren,

SARS-CoV-2 and COVID-19 Research

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. Analysis of bronchoalveolar lavage fluid samples from patients with SARS-CoV-2-induced respiratory failure suggests that SARS-CoV-2 infects alveolar macrophages to cause release of T cell chemoattractants, thereby inducing local inflammatory cytokine release and further T cell activation, ultimately resulting in a positive feedback loop that drives alveolar inflammation.