Circuits between infected macrophages and T cells in SARS-CoV-2 pneumonia
| Autor: | Darryl A. Abbott, Sean B. Smith, Ali Shilatifard, Daniel Schneider, Benjamin D. Singer, Alexander V. Misharin, Luisa Morales-Nebreda, NU Script Study Investigators, Lango Sichizya, Nikolay S. Markov, G. R. Scott Budinger, Hiam Abdala-Valencia, Ankit Bharat, Chao Qi, Elizabeth S. Malsin, Prasanth Nannapaneni, Anna Pawlowski, Helen K. Donnelly, Alvaro Donayre, Cara J. Gottardi, Yuliya Politanska, Zasu M Klug, Melissa Querrey, Suchitra Swaminathan, Mengjia Kang, Richard G Wunderink, Chiagozie O Pickens, Jacqueline M. Kruser, Hermon Kihshen, James M. Walter, Estefany R Guzman, Ziyan Lu, Nicole Borkowski, Rogan A. Grant, Isaac Goldberg, A. Christine Argento, Jon W. Lomasney |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
ARDS Time Factors T-Lymphocytes viruses medicine.medical_treatment T cell Pneumonia Viral Inflammation Article Cohort Studies Interferon-gamma 03 medical and health sciences 0302 clinical medicine Immune system Macrophages Alveolar medicine Humans RNA-Seq Respiratory system Multidisciplinary medicine.diagnostic_test SARS-CoV-2 business.industry COVID-19 respiratory system medicine.disease respiratory tract diseases Pneumonia 030104 developmental biology Bronchoalveolar lavage Cytokine medicine.anatomical_structure 030220 oncology & carcinogenesis Immunology Interferons Single-Cell Analysis medicine.symptom business Bronchoalveolar Lavage Fluid Signal Transduction |
| Zdroj: | Nature bioRxiv |
| ISSN: | 1476-4687 0028-0836 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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