| First Author | Balakrishnan A | Year | 2018 |
| Journal | Cell Death Discov | Volume | 4 |
| Pages | 3 | PubMed ID | 30062052 |
| Mgi Jnum | J:333172 | Mgi Id | MGI:7432484 |
| Doi | 10.1038/s41420-018-0068-z | Citation | Balakrishnan A, et al. (2018) Guanylate binding proteins facilitate caspase-11-dependent pyroptosis in response to type 3 secretion system-negative Pseudomonas aeruginosa. Cell Death Discov 4:3 |
| abstractText | Detection of bacterial ligands is a pre-requisite for inflammasome activation. During Pseudomonas aeruginosa infection, flagellin which is secreted through the T3SS is detected by the NLRC4 inflammasome. Activation of the NLRC4 inflammasome is believed to contribute to high IL-1beta production and pathogenicity in cystic fibrosis patients with chronic P. aeruginosa infection. Interestingly, the majority of P. aeruginosa isolated from cystic fibrosis patients with chronic airway infection are non-motile and T3SS-negative, suggesting that yet un-characterized inflammasome pathways regulate IL-1beta production in cystic fibrosis patients. Here we demonstrate the role of guanylate-binding proteins (GBPs) in regulating bacterial proliferation and inflammasome activation in response to T3SS-negative P. aeruginosa. Bacterial ligands liberated by the action of GBP2 and IRGB10 activate caspase-11 and regulate non-canonical NLRP3 inflammasome activation and IL-1beta release. Overall, our results reveal the role of caspase-11 in inhibiting bacterial proliferation and promoting IL-1beta secretion during T3SS-negative P. aeruginosa infection. This study suggests that non canonical inflammasomes might have co-evolved to detect Gram-negative bacterial pathogens that have evolved to bypass detection by canonical NLRs. |
