Natterin-mediated NLRP3 inflammasome activation in zebrafish: evolutionary insights and aquaculture implications

Natterins are pore-forming proteins with emerging roles in immunity, but their function in inflammasome activation remains unknown. Here, we demonstrate that zebrafish natterin (loc795232) is essential for NLRP3 inflammasome-mediated defense against bacterial infection. CRISPR/Cas9 knockout of natterin downregulated nlrp3 and asc expression, impaired Caspy activation, and reduced mature IL-1β secretion, exacerbating mortality in Salmonella-challenged embryos. Conversely, wild-type embryos relied on NLRP3-dependent IL-1β release to control infection and anxiety-like behaviors. Our work identifies for the first time natterin as a novel regulator of inflammasome signaling and IL-1β secretion in teleosts, with implications for evolutionary immunology and aquaculture disease management. Specifically, it opens avenues for biotechnological applications in the identification of compounds that modulate inflammasome activity, offering potential therapeutic strategies against bacterial infections in aquaculture and beyond.