分泌物
三型分泌系统
铜绿假单胞菌
炎症体
上睑下垂
NLRC4型
微生物学
效应器
生物
炎症
细菌
突变体
半胱氨酸蛋白酶1
细胞生物学
免疫学
基因
生物化学
遗传学
作者
Martin Minns,Karl Liboro,Tatiane S. Lima,Serena Abbondante,Brandon A. Miller,Michaela Marshall,Joseph Lik Hang Chau,Alicia Roistacher,Arne Rietsch,George R. Dubyak,Eric Pearlman
标识
DOI:10.1038/s41467-023-41391-7
摘要
Macrophages infected with Gram-negative bacteria expressing Type III secretion system (T3SS) activate the NLRC4 inflammasome, resulting in Gasdermin D (GSDMD)-dependent, but GSDME independent IL-1β secretion and pyroptosis. Here we examine inflammasome signaling in neutrophils infected with Pseudomonas aeruginosa strain PAO1 that expresses the T3SS effectors ExoS and ExoT. IL-1β secretion by neutrophils requires the T3SS needle and translocon proteins and GSDMD. In macrophages, PAO1 and mutants lacking ExoS and ExoT (ΔexoST) require NLRC4 for IL-1β secretion. While IL-1β release from ΔexoST infected neutrophils is also NLRC4-dependent, infection with PAO1 is instead NLRP3-dependent and driven by the ADP ribosyl transferase activity of ExoS. Genetic and pharmacologic approaches using MCC950 reveal that NLRP3 is also essential for bacterial killing and disease severity in a murine model of P. aeruginosa corneal infection (keratitis). Overall, these findings reveal a function for ExoS ADPRT in regulating inflammasome subtype usage in neutrophils versus macrophages and an unexpected role for NLRP3 in P. aeruginosa keratitis.
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