Rhinovirus-Induced Calcium Flux Triggers NLRP3 and NLRC5 Activation in Bronchial Cells

Human rhinoviruses have been linked with underlying lung disorders, such as asthma and chronic obstructive pulmonary disease, in children and adults. However, the mechanism of virus-induced airway inflammation is poorly understood. In this study, using virus deletion mutants and silencing for nucleotide-binding oligomerization domain-like receptors (NLRs), we show that the rhinovirus ion channel protein 2B triggers NLRP3 and NLRC5 inflammasome activation and IL-1 beta secretion in bronchial cells. 2B protein targets the endoplasmic reticulum and Golgi and induces Ca2+ reduction in these organelles, thereby disturbing the intracellular calcium homeostasis. NLRP3 and NLRC5 act in a cooperative manner during the inflammasome assembly by sensing intracellular Ca2+ fluxes and trigger IL-1 beta secretion. These results reveal for the first time that human rhinovirus infection in primary bronchial cells triggers inflammasome activation.