| First Author | Minns MS | Year | 2023 |
| Journal | Nat Commun | Volume | 14 |
| Issue | 1 | Pages | 5832 |
| PubMed ID | 37730693 | Mgi Jnum | J:340803 |
| Mgi Id | MGI:7530296 | Doi | 10.1038/s41467-023-41391-7 |
| Citation | Minns MS, et al. (2023) NLRP3 selectively drives IL-1beta secretion by Pseudomonas aeruginosa infected neutrophils and regulates corneal disease severity. Nat Commun 14(1):5832 |
| abstractText | 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-1beta 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-1beta secretion by neutrophils requires the T3SS needle and translocon proteins and GSDMD. In macrophages, PAO1 and mutants lacking ExoS and ExoT (DeltaexoST) require NLRC4 for IL-1beta secretion. While IL-1beta release from DeltaexoST 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. |
