| First Author | Santoni K | Year | 2022 |
| Journal | PLoS Pathog | Volume | 18 |
| Issue | 7 | Pages | e1010305 |
| PubMed ID | 35849616 | Mgi Jnum | J:327170 |
| Mgi Id | MGI:7328141 | Doi | 10.1371/journal.ppat.1010305 |
| Citation | Santoni K, et al. (2022) Caspase-1-driven neutrophil pyroptosis and its role in host susceptibility to Pseudomonas aeruginosa. PLoS Pathog 18(7):e1010305 |
| abstractText | Multiple regulated neutrophil cell death programs contribute to host defense against infections. However, despite expressing all necessary inflammasome components, neutrophils are thought to be generally defective in Caspase-1-dependent pyroptosis. By screening different bacterial species, we found that several Pseudomonas aeruginosa (P. aeruginosa) strains trigger Caspase-1-dependent pyroptosis in human and murine neutrophils. Notably, deletion of Exotoxins U or S in P. aeruginosa enhanced neutrophil death to Caspase-1-dependent pyroptosis, suggesting that these exotoxins interfere with this pathway. Mechanistically, P. aeruginosa Flagellin activates the NLRC4 inflammasome, which supports Caspase-1-driven interleukin (IL)-1beta secretion and Gasdermin D (GSDMD)-dependent neutrophil pyroptosis. Furthermore, P. aeruginosa-induced GSDMD activation triggers Calcium-dependent and Peptidyl Arginine Deaminase-4-driven histone citrullination and translocation of neutrophil DNA into the cell cytosol without inducing extracellular Neutrophil Extracellular Traps. Finally, we show that neutrophil Caspase-1 contributes to IL-1beta production and susceptibility to pyroptosis-inducing P. aeruginosa strains in vivo. Overall, we demonstrate that neutrophils are not universally resistant for Caspase-1-dependent pyroptosis. |
