A virus-specific monocyte inflammatory phenotype is induced by SARS-CoV2 at the immune-epithelial interface
Leon, J.; Michelson, D. A.; Olejnik, J.; Chowdhary, K.; Oh, H. S.; Hume, A. J.; Galvan-Pena, S.; Zhu, Y.; Chen, F.; Vijaykumar, B.; Yang, L.; Crestani, E.; Yonker, L. M.; Knipe, D. M.; Muhlberger, E.; Benoist, C.
Show abstract
Infection by SARS-CoV2 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 co-culture the interactions between infected epithelial cells and immunocytes. A strong response was induced in monocytes and B cells, with a SARS-CoV2-specific inflammatory gene cluster distinct from that seen in influenza-A or Ebola virus-infected co-cultures, 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-CoV2 proteins (Spike and some non-structural 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-CoV2 induces in epithelia.
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