Abstract

Programmed necrosis including pyroptosis and necroptosis promote host resistance against infection as it destroys the replicative niche of intracellular pathogens. In contrast, whether and how necrotic cell death drives antimicrobial defence against extracellular pathogens is less defined. To address these questions, we examined innate immune and cell death signalling upon challenge with two enteric extracellular pathogens: Yersinia pseudotuberculosis and Citrobacter rodentium. Here, we demonstrate that Y. pseudotuberculosis and C. rodentium triggers apoptotic caspase activation, which cleaves the family of gasdermin proteins to trigger pyroptosis and host defence in vivo. We further show that differential inhibition of NF-kB signalling by extracellular pathogens dictate whether myeloid cells undergo pyroptosis or necroptosis.