Fig 1.
Respiratory virus activation of the NLRP3 Inflammasome.
Respiratory viruses enter the airways and come into contact with the respiratory epithelium and alveolar macrophages (1). Infection and/or recognition of pathogen-associated molecular patterns expressed by the virus activate the innate immune response driving the release of pro-inflammatory cytokines such as IL-1β (2). Processing and secretion of IL-1β requires activation of large multimeric sensors known as the inflammasomes. NLRP3 inflammasome priming requires signal 1 activation of NF-κB driving the up-regulation of pro-IL-1β. Signal 2 activation of NLRP3 senses overall cellular stress resulting in changes in cytosolic ion concentration and formation of reactive oxygen species. This initiates binding of NLRP3 with NEK7 that licenses the complex and facilitates oligomerization with the adapter protein, Asc, and inactive pro-caspase-1. Formation of the complex produces cleaved and enzymatically active caspase-1 that can subsequently cleave and activate IL-1β as well as gasdermin D that forms membrane pores leading to pyroptosis (3). Activation of the inflammasome is essential for an effective and robust immune response against respiratory viruses (4). The potency of inflammasome activation can be a “double-edged sword” when left unrestrained leading to severe immunopathology (5). Graphics are the authors’ original work created with BioRender.com.