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

Nature. 2021 Feb;590(7847):635-641. doi: 10.1038/s41586-020-03148-w. Epub 2021 Jan 11.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Bronchoalveolar Lavage Fluid / chemistry
  • Bronchoalveolar Lavage Fluid / immunology
  • COVID-19 / genetics
  • COVID-19 / immunology*
  • COVID-19 / virology*
  • Cohort Studies
  • Humans
  • Interferon-gamma / immunology
  • Interferons / immunology
  • Interferons / metabolism
  • Macrophages, Alveolar / immunology*
  • Macrophages, Alveolar / metabolism
  • Macrophages, Alveolar / virology
  • Pneumonia, Viral / genetics
  • Pneumonia, Viral / immunology*
  • Pneumonia, Viral / virology*
  • RNA-Seq
  • SARS-CoV-2 / immunology
  • SARS-CoV-2 / pathogenicity*
  • Signal Transduction / immunology
  • Single-Cell Analysis
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Time Factors

Substances

  • Interferon-gamma
  • Interferons