Pinto Felipe Justiniano, Gusso Darlan, Bernardo Jefferson Thiago Gonçalves, Andrade-Barros Aline Ingrid, DeOcesano-Pereira Carlos, Lopes-Ferreira Monica, Lima Carla
Plataforma Zebrafish of the Laboratory of Applied Toxinology (CeTICs/FAPESP), Butantan Institute, São Paulo, Brazil.
Centre of Excellence in New Target Discovery (CENTD), Butantan Institute, São Paulo, Brazil.
Fish Shellfish Immunol. 2025 Oct;165:110508. doi: 10.1016/j.fsi.2025.110508. Epub 2025 Jun 19.
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.
纳特林蛋白是一类形成孔道的蛋白质，在免疫中发挥着新出现的作用，但其在炎性小体激活中的功能尚不清楚。在这里，我们证明斑马鱼纳特林蛋白（loc795232）对于NLRP3炎性小体介导的抗细菌感染防御至关重要。纳特林蛋白的CRISPR/Cas9基因敲除下调了nlrp3和asc的表达，损害了Caspy的激活，并减少了成熟IL-1β的分泌，加剧了沙门氏菌感染胚胎的死亡率。相反，野生型胚胎依靠NLRP3依赖性IL-1β释放来控制感染和焦虑样行为。我们的工作首次确定纳特林蛋白是硬骨鱼炎性小体信号传导和IL-1β分泌的新型调节因子，对进化免疫学和水产养殖疾病管理具有重要意义。具体而言，它为生物技术应用开辟了途径，用于鉴定调节炎性小体活性的化合物，为水产养殖及其他领域的细菌感染提供了潜在的治疗策略。
