| First Author | Meng R | Year | 2019 |
| Journal | J Biol Chem | Volume | 294 |
| Issue | 22 | Pages | 8872-8884 |
| PubMed ID | 31000631 | Mgi Jnum | J:280814 |
| Mgi Id | MGI:6368706 | Doi | 10.1074/jbc.RA118.007040 |
| Citation | Meng R, et al. (2019) High mobility group box 1 enables bacterial lipids to trigger receptor-interacting protein kinase 3 (RIPK3)-mediated necroptosis and apoptosis in mice. J Biol Chem 294(22):8872-8884 |
| abstractText | Receptor-interacting protein kinase 3 (RIPK3) is a key regulator of programmed cell death and inflammation during viral infection or sterile tissue injury. Whether and how bacterial infection also activates RIPK3-dependent immune responses remains poorly understood. Here we show that bacterial lipids (lipid IVa or lipid A) form a complex with high mobility group box 1 (HMGB1), released by activated immune cells or damaged tissue during bacterial infection, and that this complex triggers RIPK3- and TIR domain-containing adapter-inducing IFN-beta (TRIF)-dependent immune responses. We found that these responses lead to macrophage death, interleukin (IL)-1alpha release, and IL-1beta maturation. In an air-pouch inflammatory infiltration model, genetic deletion of Ripk3, Trif, or IL-1 receptor (Il-1R), or monoclonal antibody-mediated HMGB1 neutralization uniformly attenuated inflammatory responses induced by Gram-negative bacteria that release lipid IVa and lipid A. These findings uncover a previously unrecognized mechanism by which host factors and bacterial components work in concert to orchestrate immune responses. |
