Pyroptosis in Respiratory Virus Infections: A Narrative Review of Mechanisms, Pathophysiology, and Potential Therapeutic Interventions

Abstract

Pyroptosis is a mode of inflammatory cell death, characterized by cell membrane rupture and the release of pro-inflammatory cytokines and damage-associated molecular patterns (DAMPs). Pyroptosis is a critical part of the innate immune response and acts as a defense mechanism against different types of pathogens, including viruses. Several respiratory viruses, including influenza virus, respiratory syncytial virus (RSV), human metapneumovirus, and SARS-CoV-2, have been shown to trigger pyroptosis through distinct mechanisms. While pyroptosis is beneficial to the host by controlling virus replication and eliminating infected cells, the exaggerated induction of pyroptosis can be harmful and cause significant tissue damage, such as that to the lung tissue during infection with respiratory viruses. Therefore, understanding the mechanisms and the role pyroptosis plays during respiratory virus infections could lead to the development of novel therapeutic approaches to reduce the morbidity caused by these infections. In this review, we discuss the recent knowledge obtained on the pathophysiological role of pyroptosis during different respiratory viral infections as well as some experimental approaches to regulating its detrimental effects to the host.