Rhinovirus-induced epithelial RIG-I inflammasome suppresses antiviral immunity and promotes inflammation in asthma and COVID-19.

Radzikowska, Urszula; Eljaszewicz, Andrzej; Tan, Ge; Stocker, Nino; Heider, Anja; Westermann, Patrick; Steiner, Silvio; Dreher, Anita; Wawrzyniak, Paulina; Rückert, Beate; Rodriguez-Coira, Juan; Zhakparov, Damir; Huang, Mengting; Jakiela, Bogdan; Sanak, Marek; Moniuszko, Marcin; O'Mahony, Liam; Jutel, Marek; Kebadze, Tatiana; Jackson, J David; ... (2023). Rhinovirus-induced epithelial RIG-I inflammasome suppresses antiviral immunity and promotes inflammation in asthma and COVID-19. Nature communications, 14(1), p. 2329. Nature Publishing Group 10.1038/s41467-023-37470-4

Preview

Text s41467-023-37470-4.pdf - Published Version Available under License Creative Commons: Attribution (CC-BY). Download (6MB) | Preview

Rhinoviruses and allergens, such as house dust mite are major agents responsible for asthma exacerbations. The influence of pre-existing airway inflammation on the infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is largely unknown. We analyse mechanisms of response to viral infection in experimental in vivo rhinovirus infection in healthy controls and patients with asthma, and in in vitro experiments with house dust mite, rhinovirus and SARS-CoV-2 in human primary airway epithelium. Here, we show that rhinovirus infection in patients with asthma leads to an excessive RIG-I inflammasome activation, which diminishes its accessibility for type I/III interferon responses, leading to their early functional impairment, delayed resolution, prolonged viral clearance and unresolved inflammation in vitro and in vivo. Pre-exposure to house dust mite augments this phenomenon by inflammasome priming and auxiliary inhibition of early type I/III interferon responses. Prior infection with rhinovirus followed by SARS-CoV-2 infection augments RIG-I inflammasome activation and epithelial inflammation. Timely inhibition of the epithelial RIG-I inflammasome may lead to more efficient viral clearance and lower the burden of rhinovirus and SARS-CoV-2 infections.

Interest & Impact

Downloads

24 since deposited on 25 Apr 2023
15 in the past 12 months

Citations

5 Citations in Web of Science ®
6 Citations in Scopus

Search

in Google Scholar™

Services

Actions (login required)

Edit item

Actions (login required)

Edit item