Severe Acute Respiratory Syndrome Coronavirus 2-Induced Immune Activation and Death of Monocyte-Derived Human Macrophages and Dendritic Cells

J Infect Dis. 2021 Mar 3;223(5):785-795. doi: 10.1093/infdis/jiaa753.

Abstract

Studies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients and experimentally infected animals indicate a critical role for augmented expression of proinflammatory chemokines and cytokines in severe disease. Here, we demonstrate that SARS-CoV-2 infection of human monocyte-derived macrophages (MDMs) and monocyte-derived dendritic cells was abortive, but induced the production of multiple antiviral and proinflammatory cytokines (interferon-α, interferon-β, tumor necrosis factor, and interleukins 1β, 6, and 10) and a chemokine (CXCL10). Despite the lack of efficient replication in MDMs, SARS-CoV-2 induced profound interferon-mediated cell death of host cells. Macrophage activation and death were not enhanced by exposure to low levels of convalescent plasma, suggesting that antibody-dependent enhancement of infection does not contribute to cell death. Together, these results indicate that infection of macrophages and dendritic cells potentially plays a major role in coronavirus disease 2019 pathogenesis, even in the absence of productive infection.

Keywords: COVID-19; IFN; SARS-CoV-2; cell death; macrophage.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • COVID-19 / immunology
  • COVID-19 / therapy*
  • Cell Death
  • Chemokines / genetics
  • Chemokines / metabolism
  • Cytokines / genetics
  • Cytokines / metabolism
  • Dendritic Cells / immunology
  • Dendritic Cells / ultrastructure
  • Dendritic Cells / virology*
  • Humans
  • Immunization, Passive
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / virology
  • Macrophages / immunology
  • Macrophages / ultrastructure
  • Macrophages / virology*
  • Microscopy, Electron, Transmission
  • RNA, Messenger / metabolism
  • RNA, Viral / metabolism
  • SARS-CoV-2 / immunology*

Substances

  • Chemokines
  • Cytokines
  • RNA, Messenger
  • RNA, Viral

Supplementary concepts

  • COVID-19 serotherapy