T3SS translocon induces pyroptosis by direct interaction with NLRC4/NAIP inflammasome

• DOI: 10.7554/elife.100820.3
• Publication Date: 2025-02-14T17:01:00Z
• Authors: Yan Zhao; Hanshuo Zhu; Jinqian Li; Hang Xu; Li Sun
• Keywords: Pyroptosis; NLRC4

Type III secretion system (T3SS) is a virulence apparatus existing in many bacterial pathogens. Structurally, T3SS consists of the base, needle, tip, and translocon. The NLRC4 inflammasome major receptor for needle basal rod proteins. Whether other components are recognized by unclear. In this study, using Edwardsiella tarda as model intracellular pathogen, we examined T3SS−inflammasome interaction its effect on cell death. E. induced pyroptosis manner that required translocon host proteins NLRC4, NLRP3, ASC, caspase 1/4. protein EseB triggered NLRC4/NAIP-mediated binding NAIP via C-terminal region, particularly terminal 6 residues (T6R). homologs exist widely T3SS-positive bacteria share high identities T6R. Like EseB, all representatives exhibited T6R-dependent activation ability. Together these results revealed function molecular mechanism to induce suggested highly conserved inflammasome-activation