tetano
Editor, Senior Moderator
Nat Commun
. 2023 Apr 22;14(1):2329.
doi: 10.1038/s41467-023-37470-4.
Rhinovirus-induced epithelial RIG-I inflammasome suppresses antiviral immunity and promotes inflammation in asthma and COVID-19
Urszula Radzikowska[SUP] 1 2 3 [/SUP], Andrzej Eljaszewicz[SUP] 1 2 3 [/SUP], Ge Tan[SUP] 1 4 [/SUP], Nino Stocker[SUP] 1 [/SUP], Anja Heider[SUP] 1 [/SUP], Patrick Westermann[SUP] 1 [/SUP], Silvio Steiner[SUP] 5 6 7 [/SUP], Anita Dreher[SUP] 1 2 [/SUP], Paulina Wawrzyniak[SUP] 1 2 8 9 [/SUP], Beate Rückert[SUP] 1 [/SUP], Juan Rodriguez-Coira[SUP] 1 10 11 [/SUP], Damir Zhakparov[SUP] 1 [/SUP], Mengting Huang[SUP] 1 [/SUP], Bogdan Jakiela[SUP] 12 [/SUP], Marek Sanak[SUP] 12 [/SUP], Marcin Moniuszko[SUP] 3 13 [/SUP], Liam O'Mahony[SUP] 1 14 [/SUP], Marek Jutel[SUP] 15 16 [/SUP], Tatiana Kebadze[SUP] 17 18 [/SUP], J David Jackson[SUP] 19 20 [/SUP], R Michael Edwards[SUP] 17 21 [/SUP], Volker Thiel[SUP] 5 22 [/SUP], L Sebastian Johnston[SUP] 17 21 23 [/SUP], A Cezmi Akdis[SUP] #[/SUP][SUP] 1 2 [/SUP], Milena Sokolowska[SUP] #[/SUP][SUP] 24 25 [/SUP]
Affiliations
Abstract
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.
. 2023 Apr 22;14(1):2329.
doi: 10.1038/s41467-023-37470-4.
Rhinovirus-induced epithelial RIG-I inflammasome suppresses antiviral immunity and promotes inflammation in asthma and COVID-19
Urszula Radzikowska[SUP] 1 2 3 [/SUP], Andrzej Eljaszewicz[SUP] 1 2 3 [/SUP], Ge Tan[SUP] 1 4 [/SUP], Nino Stocker[SUP] 1 [/SUP], Anja Heider[SUP] 1 [/SUP], Patrick Westermann[SUP] 1 [/SUP], Silvio Steiner[SUP] 5 6 7 [/SUP], Anita Dreher[SUP] 1 2 [/SUP], Paulina Wawrzyniak[SUP] 1 2 8 9 [/SUP], Beate Rückert[SUP] 1 [/SUP], Juan Rodriguez-Coira[SUP] 1 10 11 [/SUP], Damir Zhakparov[SUP] 1 [/SUP], Mengting Huang[SUP] 1 [/SUP], Bogdan Jakiela[SUP] 12 [/SUP], Marek Sanak[SUP] 12 [/SUP], Marcin Moniuszko[SUP] 3 13 [/SUP], Liam O'Mahony[SUP] 1 14 [/SUP], Marek Jutel[SUP] 15 16 [/SUP], Tatiana Kebadze[SUP] 17 18 [/SUP], J David Jackson[SUP] 19 20 [/SUP], R Michael Edwards[SUP] 17 21 [/SUP], Volker Thiel[SUP] 5 22 [/SUP], L Sebastian Johnston[SUP] 17 21 23 [/SUP], A Cezmi Akdis[SUP] #[/SUP][SUP] 1 2 [/SUP], Milena Sokolowska[SUP] #[/SUP][SUP] 24 25 [/SUP]
Affiliations
- PMID: 37087523
- DOI: 10.1038/s41467-023-37470-4
Abstract
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.