Flagellin from Pseudomonas aeruginosa increases the expression of the SARS-CoV2 entry protease TMPRSS2 in airway epithelial cells (Équipe Corvol)

BioRxiv

The major challenge of the COVID-19 health crisis is to identify the factors of susceptibility to SARS-Cov2 in order to adapt the recommendations to the populations and to reduce the risk of getting COVID-19 to the most vulnerable people especially those having chronic respiratory diseases (CRD) including cystic fibrosis (CF) and chronic pulmonary respiratory diseases (COPD). Airway epithelial cells (AEC) are playing a critical role in the immune response and in COVID-19 severity. SARS-CoV-2 infects the airways through ACE2 receptor and the host protease TMPRSS2 was shown to play a major role in SARS-CoV-2 infectivity.

In this report we showed that Pseudomonas aeruginosa and its virulence factor flagellin (Fla-PA), a ligand of Toll-Like receptor 5 are able to increase TMPRSS2 expression in control and CF AEC. In contrast, no effect was observed with recombinant Salmonella typhimurium flagellin, used as an adjuvant in the clinical development of new vaccines against respiratory viruses. Considering the urgency of the health situation, this result is of major significance for patients with CRD (COPD, CF) which are frequently infected and colonized by P. aeruginosa during the course of the disease. In the general population, a P. aeruginosa ventilator-associated pneumonia in SARS-CoV-2 patients under intubation in intensive care units could be also deleterious and should be monitored with care.