Flagellin From Pseudomonas aeruginosa Modulates SARS-CoV-2 Infectivity in Cystic Fibrosis Airway Epithelial Cells by Increasing TMPRSS2 Expression - Archive ouverte HAL
Article Dans Une Revue Frontiers in Immunology Année : 2021

Flagellin From Pseudomonas aeruginosa Modulates SARS-CoV-2 Infectivity in Cystic Fibrosis Airway Epithelial Cells by Increasing TMPRSS2 Expression

Manon Ruffin
  • Fonction : Auteur
Jeanne Bigot
  • Fonction : Auteur
Claire Calmel
  • Fonction : Auteur
Julia Mercier
  • Fonction : Auteur
Maëlle Givelet
  • Fonction : Auteur
Justine Oliva
Andrés Pizzorno
  • Fonction : Auteur
Manuel Rosa-Calatrava
Harriet Corvol
Viviane Balloy
  • Fonction : Auteur
Olivier Terrier

Résumé

In the coronavirus disease 2019 (COVID-19) health crisis, one major challenge is to identify the susceptibility factors of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) in order to adapt the recommendations for populations, as well as to reduce the risk of COVID-19 development in the most vulnerable people, especially patients with chronic respiratory diseases such as cystic fibrosis (CF). Airway epithelial cells (AECs) play a critical role in the modulation of both immune responses and COVID-19 severity. SARS-CoV-2 infects the airway through the receptor angiotensin-converting enzyme 2, and a host protease, transmembrane serine protease 2 (TMPRSS2), plays a major role in SARS-CoV-2 infectivity. Here, we show that Pseudomonas aeruginosa increases TMPRSS2 expression, notably in primary AECs with deficiency of the ion channel CF transmembrane conductance regulator (CFTR). Further, we show that the main component of P. aeruginosa flagella, the protein flagellin, increases TMPRSS2 expression in primary AECs and Calu-3 cells, through activation of Toll-like receptor-5 and p38 MAPK. This increase is particularly seen in Calu-3 cells deficient for CFTR and is associated with an intracellular increased level of SARS-CoV-2 infection, however, with no effect on the amount of virus particles released. Considering the urgency of the COVID-19 health crisis, this result may be of clinical significance for CF patients, who are frequently infected with and colonized by P. aeruginosa during the course of CF and might develop COVID-19.
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hal-03829159 , version 1 (25-01-2023)

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Manon Ruffin, Jeanne Bigot, Claire Calmel, Julia Mercier, Maëlle Givelet, et al.. Flagellin From Pseudomonas aeruginosa Modulates SARS-CoV-2 Infectivity in Cystic Fibrosis Airway Epithelial Cells by Increasing TMPRSS2 Expression. Frontiers in Immunology, 2021, 12, ⟨10.3389/fimmu.2021.714027⟩. ⟨hal-03829159⟩
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