PLOS Pathogens: Burning Down the House: Cellular Actions during Pyroptosis

Under threat of pathogen invasion, timely initiation of inflammation is a critical first step in generating a protective immune response. One major obstacle for the immune system is discriminating pathogenic microbes from non-pathogenic microbiota. Some members of the nucleotide-binding oligomerization domain-like receptor (NLR) family of pattern recognition receptors accomplish this distinction based on localization—typically, only pathogens deliver NLR ligands into the cytosol, where these receptors are localized. Ultimately, these NLRs initiate assembly of an inflammasome complex that activates the proteases caspase-1 and caspase-11. These caspases were originally identified for their role in IL-1β processing and release but are now known to direct additional important cellular processes during infection, inflammatory disorders, and response to injury. In this brief review, we enumerate these emerging pathways and highlight their roles in disease.