Influenza A viruses (IAV) trigger contagious acute respiratory diseases. A better understanding of the molecular mechanisms of IAV pathogenesis and host immune responses is required for the development of more efficient treatments of severe influenza. Calpains are intracellular proteases that participate to diverse cellular responses, including inflammation. Here, we used in vitro and in vivo approaches to investigate the role of calpains signalling in IAV pathogenesis. Calpain expression and activity were found altered in IAV-infected bronchial epithelial cells. Using siRNA gene silencing, specific synthetic inhibitors of calpains and mice overexpressing calpastatin, we found that calpain inhibition dampens IAV replication as well as IAV-triggered secretion of pro-inflammatory mediators and leukocyte infiltration. Remarkably, calpain inhibition has a protective impact in IAV infection as it significantly reduced mortality of mice challenged not only by seasonal H3N2- but also by hypervirulent H5N1 IAV strains. Hence, our study suggests that calpains are promising therapeutic target for treating IAV acute pneumonia.
- signal transduction
- Copyright © 2015, American Journal of Physiology - Lung Cellular and Molecular Physiology