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Cited by 727

The DOI matches its Crossref record; 33 of the 33 references it cites were found in a registry or an index.

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

Open access
Grant, Rogan A., Morales-Nebreda, Luisa, Markov, Nikolay S., Swaminathan, Suchitra, Querrey, Melissa, Guzman, Estefany R., Abbott, Darryl A., Donnelly, Helen K., Donayre, Alvaro, Goldberg, Isaac A., Klug, Zasu M., Borkowski, Nicole, Lu, Ziyan, Kihshen, Hermon, Politanska, Yuliya, Sichizya, Lango, Kang, Mengjia, Shilatifard, Ali, Qi, Chao, Lomasney, Jon W., Argento, A. Christine, Kruser, Jacqueline M., Malsin, Elizabeth S., Pickens, Chiagozie O., Smith, Sean B., Walter, James M., Pawlowski, Anna E., Schneider, Daniel, Nannapaneni, Prasanth, Abdala-Valencia, Hiam, Bharat, Ankit, Gottardi, Cara J., Budinger, G. R. Scott, Misharin, Alexander V., Singer, Benjamin D., Wunderink, Richard G., The NU SCRIPT Study Investigators, Grant, Rogan A., Morales-Nebreda, Luisa, Markov, Nikolay S., Swaminathan, Suchitra, Querrey, Melissa, Guzman, Estefany R., Abbott, Darryl A., Donnelly, Helen K., Donayre, Alvaro, Goldberg, Isaac A., Klug, Zasu M., Borkowski, Nicole, Lu, Ziyan, Kihshen, Hermon, Politanska, Yuliya, Sichizya, Lango, Kang, Mengjia, Shilatifard, Ali, Qi, Chao, Lomasney, Jon W., Argento, A. Christine, Kruser, Jacqueline M., Malsin, Elizabeth S., Pickens, Chiagozie O., Smith, Sean B., Walter, James M., Pawlowski, Anna E., Schneider, Daniel, Nannapaneni, Prasanth, Abdala-Valencia, Hiam, Bharat, Ankit, Gottardi, Cara J., Budinger, G. R. Scott, Misharin, Alexander V., Singer, Benjamin D., Wunderink, Richard G., Wagh, Ajay A., Hauser, Alan R., Wolfe, Alexis Rose, Thakrar, Anjali, Yeldandi, Anjana V., Wang, Ann A., Levenson, Anne R., Joudi, Anthony M., Tran, Betty, Gao, Catherine A., Kurihara, Chitaru, Schroedl, Clara J., Horvath, Curt M., Meza, Daniel, Odell, David D., Kamp, David W., Winter, Deborah R., Ozer, Egon A., Shanes, Elisheva D., Bartom, Elizabeth T., Rendleman, Emily J., Leibenguth, Emily M., Wehbe, Firas, Liu, Gabrielle Y., Gadhvi, Gaurav T., Navarro, Heliodoro Tejedor, Sznajder, Jacob I., Dematte, Jane E., Le, Jasmine, Arnold, Jason M., Du, Joanne C., Coleman, John, Bailey, Joseph I., Deters, Joseph S., Fiala, Justin A., Starren, Justin, Ridge, Karen M., Secunda, Katharine, Aren, Kathleen, Gates, Khalilah L., Todd, Kristy, Gradone, Lindsey D., Textor, Lindsey N., Wolfe, Lisa F., Pesce, Lorenzo L., Nunes Amaral, Luís A., Rosenbaum, Madeline L., Kandpal, Manoj, Jain, Manu, Sala, Marc A., Saine, Mark, Carns, Mary, Alexander, Michael J., Cuttica, Michael J., Prickett, Michelle H., Khan, Nabiha H., Chandel, Navdeep S., Soulakis, Nicholas D., Rivas, Orlyn R., Seed, Patrick C., Reyfman, Paul A., Go, Pearl D., Sporn, Peter H. S., Cooper, Phillip R., Tomic, Rade, Patel, Radhika, Garza-Castillon, Rafael, Kalhan, Ravi, Morimoto, Richard I., Mylvaganam, Ruben J., Kim, Samuel S., Gatesy, Samuel W. M., Thakkar, Sanket, Ben Maamar, Sarah, Han, SeungHye, Rosenberg, Sharon R., Nozick, Sophia, Green, Stefan J., Russell, Susan R., Poor, Taylor A., Zak, Taylor J., Lombardo, Theresa A., Stoeger, Thomas, Shamaly, Todd, Ren, Ziyou·2021·Nature
DOI 10.1038/s41586-020-03148-w
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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. 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.

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Authors
Grant, R. A., Morales-Nebreda, L., Markov, N. S., Swaminathan, S., Querrey, M., Guzman, E. R., Abbott, D. A., Donnelly, H. K., Donayre, A., Goldberg, I. A., Klug, Z. M., Borkowski, N., Lu, Z., Kihshen, H., Politanska, Y., Sichizya, L., Kang, M., Shilatifard, A., Qi, C., Lomasney, J. W., Argento, A. C., Kruser, J. M., Malsin, E. S., Pickens, C. O., Smith, S. B., Walter, J. M., Pawlowski, A. E., Schneider, D., Nannapaneni, P., Abdala-Valencia, H., Bharat, A., Gottardi, C. J., Budinger, G. R. S., Misharin, A. V., Singer, B. D., Wunderink, R. G., The NU SCRIPT Study Investigators, Grant, R. A., Morales-Nebreda, L., Markov, N. S., Swaminathan, S., Querrey, M., Guzman, E. R., Abbott, D. A., Donnelly, H. K., Donayre, A., Goldberg, I. A., Klug, Z. M., Borkowski, N., Lu, Z., Kihshen, H., Politanska, Y., Sichizya, L., Kang, M., Shilatifard, A., Qi, C., Lomasney, J. W., Argento, A. C., Kruser, J. M., Malsin, E. S., Pickens, C. O., Smith, S. B., Walter, J. M., Pawlowski, A. E., Schneider, D., Nannapaneni, P., Abdala-Valencia, H., Bharat, A., Gottardi, C. J., Budinger, G. R. S., Misharin, A. V., Singer, B. D., Wunderink, R. G., Wagh, A. A., Hauser, A. R., Wolfe, A. R., Thakrar, A., Yeldandi, A. V., Wang, A. A., Levenson, A. R., Joudi, A. M., Tran, B., Gao, C. A., Kurihara, C., Schroedl, C. J., Horvath, C. M., Meza, D., Odell, D. D., Kamp, D. W., Winter, D. R., Ozer, E. A., Shanes, E. D., Bartom, E. T., Rendleman, E. J., Leibenguth, E. M., Wehbe, F., Liu, G. Y., Gadhvi, G. T., Navarro, H. T., Sznajder, J. I., Dematte, J. E., Le, J., Arnold, J. M., Du, J. C., Coleman, J., Bailey, J. I., Deters, J. S., Fiala, J. A., Starren, J., Ridge, K. M., Secunda, K., Aren, K., Gates, K. L., Todd, K., Gradone, L. D., Textor, L. N., Wolfe, L. F., Pesce, L. L., Nunes Amaral, L. A., Rosenbaum, M. L., Kandpal, M., Jain, M., Sala, M. A., Saine, M., Carns, M., Alexander, M. J., Cuttica, M. J., Prickett, M. H., Khan, N. H., Chandel, N. S., Soulakis, N. D., Rivas, O. R., Seed, P. C., Reyfman, P. A., Go, P. D., Sporn, P. H. S., Cooper, P. R., Tomic, R., Patel, R., Garza-Castillon, R., Kalhan, R., Morimoto, R. I., Mylvaganam, R. J., Kim, S. S., Gatesy, S. W. M., Thakkar, S., Ben Maamar, S., Han, S., Rosenberg, S. R., Nozick, S., Green, S. J., Russell, S. R., Poor, T. A., Zak, T. J., Lombardo, T. A., Stoeger, T., Shamaly, T., & Ren, Z.
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2021-01-11
Volume
590
Issue
7847
Pages
635-641
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/s41586-020-03148-w
OpenAlex
W3120857229
Cited by
727
References
33
FWCI
44.79
Type
journal article
Language
en
Open access
bronze

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