| First Author | Karki R | Year | 2020 |
| Journal | J Immunol | Volume | 204 |
| Issue | 9 | Pages | 2514-2522 |
| PubMed ID | 32205422 | Mgi Jnum | J:289674 |
| Mgi Id | MGI:6431946 | Doi | 10.4049/jimmunol.1901508 |
| Citation | Karki R, et al. (2020) IRF8 Regulates Gram-Negative Bacteria-Mediated NLRP3 Inflammasome Activation and Cell Death. J Immunol 204(9):2514-2522 |
| abstractText | Inflammasomes are intracellular signaling complexes that are assembled in response to a variety of pathogenic or physiologic stimuli to initiate inflammatory responses. Ubiquitously present LPS in Gram-negative bacteria induces NLRP3 inflammasome activation that requires caspase-11. We have recently demonstrated that IFN regulatory factor (IRF) 8 was dispensable for caspase-11-mediated NLRP3 inflammasome activation during LPS transfection; however, its role in Gram-negative bacteria-mediated NLRP3 inflammasome activation remains unknown. In this study, we found that IRF8 promotes NLRP3 inflammasome activation in murine bone marrow-derived macrophages (BMDMs) infected with Gram-negative bacteria such as Citrobacter rodentium, Escherichia coli, or Pseudomonas aeruginosa mutant strain DeltapopB Moreover, BMDMs deficient in IRF8 showed substantially reduced caspase-11 activation and gasdermin D cleavage, which are required for NLRP3 inflammasome activation. Mechanistically, IRF8-mediated phosphorylation of IRF3 was required for Ifnb transcription, which in turn triggered the caspase-11-dependent NLRP3 inflammasome activation in the infected BMDMs. Overall, our findings suggest that IRF8 promotes NLRP3 inflammasome activation during infection with Gram-negative bacteria. |
