Journal Article

A virus-specific monocyte inflammatory phenotype is induced by SARS-CoV-2 at the immune–epithelial interface

Leon, Juliette, Olejnik, Judith, Mühlberger, Elke, Chen, Felicia, Yonker, Lael M., Michelson, Daniel A., Crestani, Elena, Yang, Liang, Knipe, David M., Galván-Peña, Silvia, Zhu, Yangyang, Hume, Adam J., Chowdhary, Kaitavjeet, Oh, Hyung Suk, Vijaykumar, Brinda, Benoist, Christophe

2022

Overview

Infection by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) provokes a potentially fatal pneumonia with multiorgan failure, and high systemic inflammation. To gain mechanistic insight and ferret out the root of this immune dysregulation, we modeled, by in vitro coculture, the interactions between infected epithelial cells and immunocytes. A strong response was induced in monocytes and B cells, with a SARS-CoV-2–specific inflammatory gene cluster distinct from that seen in influenza A or Ebola virus-infected cocultures, and which reproduced deviations reported in blood or lung myeloid cells from COVID-19 patients. A substantial fraction of the effect could be reproduced after individual transfection of several SARS-CoV-2 proteins (Spike and some nonstructural proteins), mediated by soluble factors, but not via transcriptional induction. This response was greatly muted in monocytes from healthy children, perhaps a clue to the age dependency of COVID-19. These results suggest that the inflammatory malfunction in COVID-19 is rooted in the earliest perturbations that SARS-CoV-2 induces in epithelia.

• Publisher: National Academy of Sciences
• Subject: Adult / B-Lymphocytes - immunology / Biological Sciences / Child / Coculture Techniques / Coronaviruses / COVID-19 / COVID-19 - immunology / COVID-19 - pathology / Ebolavirus - pathogenicity / Epithelial cells / Epithelial Cells - immunology / Epithelial Cells - virology / Epithelium / Gene Expression Profiling / Humans / Immunology and Inflammation / Inflammation / Influenza A / Influenza A virus - pathogenicity / Lung - immunology / Lymphocytes B / Monocytes / Monocytes - immunology / Myeloid cells / Myeloid Cells - immunology / Nonstructural proteins / Perturbation / Phenotypes / Proteins / SARS-CoV-2 - pathogenicity / Severe acute respiratory syndrome coronavirus 2 / Species Specificity / Transcription factors / Transfection / Viral diseases / Viral Proteins - immunology / Viruses