Research
| Title： | Grass carp Hnf4β orchestrates antibacterial defense via the AIF/Hnf4α/ caspase 3 signaling axis |
|---|---|
| First author： | Yan, Dong; Chang, Ming Xian |
| Journal： | FISH & SHELLFISH IMMUNOLOGY |
| Years： | 2025 |
| DOI： | 10.1016/j.fsi.2025.110534 |
| Abstract： | Hepatocyte nuclear factor 4 (HNF4), a transcription factor family critical for hepatic development and metabolic homeostasis, consists of three isoforms (HNF4 alpha, HNF4 beta, HNF4 gamma). While HNF4 alpha and HNF4 gamma are evolutionarily conserved across vertebrates, HNF4 beta is restricted to teleosts, amphibians and birds, with its antimicrobial function poorly characterized. Here, we investigate the role of grass carp Hnf4 beta (gcHnf4 beta) in response to Aeromonas salmonicida infection, uncovering a novel antibacterial signaling axis. Overexpression of gcHnf4 beta significantly attenuates bacterial proliferation and augments Ctenopharyngodon idella kidney (CIK) cell viability through transcriptional upregulation of caspase 3, caspase 9 and apoptosis-inducing factor (AIF). Mechanistically, gcHnf4 beta acts as a transcriptional hub, directly interacting with AIF and forming a ternary complex with gcHnf4 alpha to indirectly engage caspase 3. Subcellular dynamics show nuclear retention of gcHnf4 beta during infection, concurrent with cytoplasmic-to-nuclear translocation of AIF/caspase 3 and their co-localization in the nucleus. Functional validation reveals that AIF knockdown or caspase 3 inhibition abolishes antibacterial activity mediated by gcHnf4 beta, whereas caspase 9 inhibition does not. Our findings establish gcHnf4 beta as a critical regulator of antimicrobial immunity, providing novel insights into host-pathogen interactions and potential targets for aquaculture disease control. |
