State Key Laboratory of Biocontrol, School of Marine Sciences, Sun Yat-sen University, Guangzhou, China.
Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), Zhuhai, China.
Front Immunol. 2022 Aug 19;13:977327. doi: 10.3389/fimmu.2022.977327. eCollection 2022.
Stimulator of interferon genes (STING) is crucial for the innate immune to defend against pathogenic infections. Our previous study showed that a STING homolog from Litopenaeus vannamei (LvSTING) was involved in antibacterial response regulating antimicrobial peptides (AMPs). Nevertheless, how LvSTING induces AMPs expression to inhibit bacterial infection remains unknown. Herein, we revealed that the existence of a STING-IKKβ-Relish-AMPs axis in shrimp that was essential for opposing to Vibrio parahaemolyticus invasion. We observed that LvRelish was essential for host defense against V. parahaemolyticus infection inducing several AMPs, such as LvALF1, LvCRU1, LvLYZ1 and LvPEN4. Knockdown of LvSTING or LvIKKβ led to the attenuated phosphorylation and diminished nuclear translocation of LvRelish, as well as the impaired expression levels of LvRelish-regulated AMPs. Accordingly, shrimps with knockdown of LvSTING or LvIKKβ or both were vulnerable to V. parahaemolyticus infection. Finally, LvSTING could recruit LvRelish and LvIKKβ to form a complex, which synergistically induced the promoter activity of several AMPs . Taken together, our results demonstrated that the shrimp STING-IKKβ-Relish-AMPs axis played a critical role in the defense against bacterial infection, and provided some insights into the development of disease prevention strategies in shrimp culture.
干扰素基因刺激蛋白(STING)对于先天免疫防御病原体感染至关重要。我们之前的研究表明,凡纳滨对虾的 STING 同源物(LvSTING)参与了调节抗菌肽(AMPs)的抗菌反应。然而,LvSTING 如何诱导 AMPs 表达来抑制细菌感染仍然未知。在此,我们揭示了虾中存在 STING-IKKβ-Relish-AMPs 轴,该轴对于抵抗副溶血弧菌入侵至关重要。我们观察到 LvRelish 对于宿主抵抗副溶血弧菌感染和诱导几种 AMPs(如 LvALF1、LvCRU1、LvLYZ1 和 LvPEN4)至关重要。LvSTING 或 LvIKKβ 的敲低导致 LvRelish 的磷酸化减弱和核转位减少,以及 LvRelish 调节的 AMPs 的表达水平受损。因此,敲低 LvSTING 或 LvIKKβ 或两者都使虾易受副溶血弧菌感染。最后,LvSTING 可以募集 LvRelish 和 LvIKKβ 形成复合物,协同诱导几种 AMPs 的启动子活性。总之,我们的结果表明,虾的 STING-IKKβ-Relish-AMPs 轴在抵抗细菌感染中发挥着关键作用,并为虾养殖中疾病预防策略的发展提供了一些思路。