Enteropathogenic Escherichia coli Stimulates Effector-Driven Rapid Caspase-4 Activation in Human Macrophages

摘要: Summary Microbial infections can stimulate the assembly of inflammasomes, which activate caspase-1. The gastrointestinal pathogen enteropathogenic Escherichia coli (EPEC) causes localized actin polymerization in host cells. Actin requires binding bacterial adhesin intimin to Tir, is delivered cells via a type 3 secretion system (T3SS). We show that EPEC induces T3SS-dependent rapid non-canonical NLRP3 inflammasome activation in human macrophages. Notably, caspase-4 activation by triggers pyroptosis and cytokine processing through NLRP3-caspase-1 inflammasome. Mechanistically, detection LPS EPEC-induced polymerization, either Tir tyrosine phosphorylation phosphotyrosine-binding adaptor NCK or NCK-mimicking effector TccP. An engineered E. coli K12 could reconstitute Tir-intimin signaling, necessary sufficient for activation, ruling out involvement other virulence factors. Our studies reveal crosstalk between caspase-1 cooperatively stimulated effector-driven polymerization.