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Circuits between infected macrophages and T cells in SARS-CoV-2 pneumonia
- Source :
- Nature, bioRxiv
- Publication Year :
- 2021
-
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.
- Subjects :
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 14764687 and 00280836
- Volume :
- 590
- Issue :
- 7847
- Database :
- OpenAIRE
- Journal :
- Nature
- Accession number :
- edsair.doi.dedup.....15d156b55299235ad6e217891e2a6166