tetano
Editor, Senior Moderator
Proc Natl Acad Sci U S A
. 2022 Jan 4;119(1):e2116853118.
doi: 10.1073/pnas.2116853118.
A virus-specific monocyte inflammatory phenotype is induced by SARS-CoV-2 at the immune-epithelial interface
Juliette Leon[SUP] 1 2 [/SUP], Daniel A Michelson[SUP] 1 [/SUP], Judith Olejnik[SUP] 3 4 [/SUP], Kaitavjeet Chowdhary[SUP] 1 [/SUP], Hyung Suk Oh[SUP] 5 [/SUP], Adam J Hume[SUP] 3 4 [/SUP], Silvia Galván-Peña[SUP] 1 [/SUP], Yangyang Zhu[SUP] 1 [/SUP], Felicia Chen[SUP] 1 [/SUP], Brinda Vijaykumar[SUP] 1 [/SUP], Liang Yang[SUP] 1 [/SUP], Elena Crestani[SUP] 6 7 [/SUP], Lael M Yonker[SUP] 8 [/SUP], David M Knipe[SUP] 5 [/SUP], Elke Mühlberger[SUP] 3 4 [/SUP], Christophe Benoist[SUP] 9 [/SUP]
Affiliations
Abstract
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.
Keywords: COVID-19; cytokine storm; interferon.
. 2022 Jan 4;119(1):e2116853118.
doi: 10.1073/pnas.2116853118.
A virus-specific monocyte inflammatory phenotype is induced by SARS-CoV-2 at the immune-epithelial interface
Juliette Leon[SUP] 1 2 [/SUP], Daniel A Michelson[SUP] 1 [/SUP], Judith Olejnik[SUP] 3 4 [/SUP], Kaitavjeet Chowdhary[SUP] 1 [/SUP], Hyung Suk Oh[SUP] 5 [/SUP], Adam J Hume[SUP] 3 4 [/SUP], Silvia Galván-Peña[SUP] 1 [/SUP], Yangyang Zhu[SUP] 1 [/SUP], Felicia Chen[SUP] 1 [/SUP], Brinda Vijaykumar[SUP] 1 [/SUP], Liang Yang[SUP] 1 [/SUP], Elena Crestani[SUP] 6 7 [/SUP], Lael M Yonker[SUP] 8 [/SUP], David M Knipe[SUP] 5 [/SUP], Elke Mühlberger[SUP] 3 4 [/SUP], Christophe Benoist[SUP] 9 [/SUP]
Affiliations
- PMID: 34969849
- DOI: 10.1073/pnas.2116853118
Abstract
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.
Keywords: COVID-19; cytokine storm; interferon.