Alveolitis in severe SARS-CoV-2 pneumonia is driven by self-sustaining circuits between infected alveolar macrophages and T cells
Alveolitis in severe SARS-CoV-2 pneumonia is driven by self-sustaining circuits between infected alveolar macrophages and T cells
Abstract Some patients infected with Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) develop severe pneumonia and the acute respiratory distress syndrome (ARDS) [1]. 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 [2]. We collected bronchoalveolar lavage fluid samples from 86 patients with SARS-CoV-2-induced respiratory failure and 252 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 in 5 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 at the onset of mechanical ventilation, the alveolar space is persistently enriched in alveolar macrophages and T cells without neutrophilia. Bulk and single cell transcriptomic profiling suggest SARS-CoV-2 infects alveolar macrophages that respond by recruiting T cells. These T cells release interferon-gamma to induce inflammatory cytokine release from alveolar macrophages and further promote T cell recruitment. Our results suggest SARS-CoV-2 causes a slowly unfolding, spatially-limited alveolitis in which alveolar macrophages harboring SARS-CoV-2 transcripts and T cells form a positive feedback loop that drives progressive alveolar inflammation. This manuscript is accompanied by an online resource: https://www.nupulmonary.org/covid-19/ One sentence summarySARS-CoV-2-infected alveolar macrophages form positive feedback loops with T cells in patients with severe COVID-19.
Abdala-Valencia Hiam、Budinger GR Scott、for The NU SCRIPT Study Investigators、Goldberg Isaac A.、Klug Zasu M.、Borkowski Nicole、Kihshen Hermon、Politanska Yuliya、Sichizya Lango、Qi Chao、Kruser Jacqueline M.、Malsin Elizabeth S.、Walter James M.、Pawlowski Anna E.、Schneider Daniel、Donayre Alvaro、Singer Benjamin D.、Pickens Chiagozie O.、Guzman Estefany R.、Abbott Darryl A.、Wunderink Richard G.、Argento A. Christine、Misharin Alexander V.、Nannapaneni Prasanth、Bharat Ankit、Shilatifard Ali、Donnelly Helen K.、Grant Rogan A.、Smith Sean、Gottardi Cara J.、Kang Mengjia、Lu Ziyan、Swaminathan Suchitra、Morales-Nebreda Luisa、Markov Nikolay S.
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern UniversityDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern UniversityDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern UniversityDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern UniversityDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern UniversityDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern UniversityDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern UniversityDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern UniversityDepartment of Pathology, Feinberg School of Medicine, Northwestern UniversityDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern UniversityDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern UniversityDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern UniversityClinical and Translational Sciences Institute, Feinberg School of Medicine, Northwestern UniversityClinical and Translational Sciences Institute, Feinberg School of Medicine, Northwestern UniversityDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern UniversityDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University||Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University||Simpson Querrey Center for Epigenetics, Feinberg School of Medicine, Northwestern UniversityDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern UniversityRobert H Lurie Comprehensive Cancer Research Center, Feinberg School of Medicine, Northwestern UniversityRobert H Lurie Comprehensive Cancer Research Center, Feinberg School of Medicine, Northwestern UniversityDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University||Simpson Querrey Center for Epigenetics, Feinberg School of Medicine, Northwestern UniversityDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern UniversityDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern UniversityClinical and Translational Sciences Institute, Feinberg School of Medicine, Northwestern UniversityDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University||Division of Thoracic Surgery, Department of Surgery, Feinberg School of Medicine, Northwestern UniversityDepartment of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University||Simpson Querrey Center for Epigenetics, Feinberg School of Medicine, Northwestern UniversityDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern UniversityDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern UniversityDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern UniversityDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern UniversityDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern UniversityDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern UniversityDivision of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University||Robert H Lurie Comprehensive Cancer Research Center, Feinberg School of Medicine, Northwestern UniversityDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern UniversityDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University
医学研究方法基础医学内科学
Abdala-Valencia Hiam,Budinger GR Scott,for The NU SCRIPT Study Investigators,Goldberg Isaac A.,Klug Zasu M.,Borkowski Nicole,Kihshen Hermon,Politanska Yuliya,Sichizya Lango,Qi Chao,Kruser Jacqueline M.,Malsin Elizabeth S.,Walter James M.,Pawlowski Anna E.,Schneider Daniel,Donayre Alvaro,Singer Benjamin D.,Pickens Chiagozie O.,Guzman Estefany R.,Abbott Darryl A.,Wunderink Richard G.,Argento A. Christine,Misharin Alexander V.,Nannapaneni Prasanth,Bharat Ankit,Shilatifard Ali,Donnelly Helen K.,Grant Rogan A.,Smith Sean,Gottardi Cara J.,Kang Mengjia,Lu Ziyan,Swaminathan Suchitra,Morales-Nebreda Luisa,Markov Nikolay S..Alveolitis in severe SARS-CoV-2 pneumonia is driven by self-sustaining circuits between infected alveolar macrophages and T cells[EB/OL].(2025-03-28)[2025-06-19].https://www.biorxiv.org/content/10.1101/2020.08.05.238188.点此复制
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