The characterization of BCL-xL displays a non-apoptotic role in suppression of NLRP1 inflammasome assembly in common carp (Cyprinus carpio L.)

IF 4.1 2区农林科学 Q1 FISHERIES

Fish & shellfish immunology Pub Date : 2024-11-01 DOI:10.1016/j.fsi.2024.110001

Hong Jiang , Jiahui Zhang , Tingting Liu , Xinping Chen , Guiwen Yang , Hua Li

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引用次数: 0

Abstract

The NLRP1 inflammasome is a crucial muti-protein complex in the host anti-pathogen immune response. The previous studies have revealed that the anti-apoptotic protein BCL-xL played a non-apoptotic role by impeding the activation of NLRP1 inflammasome in mammals. However, the potential role of BCL-xL in regulating the inflammasome in fish remains unclear. In the present study, the BCL-xL (CcBCL-xL) was cloned from the head kidney of common carp (Cyprinus carpio L.), and its regulatory effect on the NLRP1 inflammasome was explored. It was found that CcBCL-xL predominantly localized in the brain, spleen and head kidney of common carp, and upon stimulation with Aeromonas hydrophila (A. hydrophila), Edwardsiella tarda (E. tarda), or spring viremia of carp virus (SVCV), the expression of CcBCL-xL significantly increased in multiple immune organs. The interaction between CcBCL-xL and CcNLRP1 was confirmed by co-immunoprecipitation and immunofluorescence. Meanwhile, we also found that CcBCL-xL significantly inhibited the assembly of the CcNLRP1 inflammasome, through ASC oligomerization, ASC specks formation and cytotoxicity experiments. Furthermore, our results revealed that CcBCL-xL interacted with the NACHT, LRR, FIIND, and CARD domains of CcNLRP1. Taken together, the results provide a theoretical foundation for further exploring the regulatory mechanism of NLRP1, and for the prevention and treatment of infectious diseases in fish.

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BCL-xL在抑制鲤鱼（Cyprinus carpio L.）NLRP1炎症小体组装方面发挥了非凋亡作用。

NLRP1 炎症小体是宿主抗病原体免疫反应中一个重要的突变蛋白复合物。先前的研究发现，在哺乳动物体内，抗凋亡蛋白 BCL-xL 通过阻碍 NLRP1 炎症小体的活化发挥非凋亡作用。然而，BCL-xL 在调节鱼类炎症小体中的潜在作用仍不清楚。本研究从鲤鱼头肾中克隆了 BCL-xL（CcBCL-xL），并探讨了它对 NLRP1 炎症小体的调控作用。研究发现，CcBCL-xL 主要定位于鲤鱼的脑、脾和头肾，在嗜水气单胞菌（A. hydrophila）、Edwardsiella tarda（E. tarda）或春季鲤鱼病毒（SVCV）的刺激下，CcBCL-xL 在多个免疫器官中的表达显著增加。通过共沉淀和免疫荧光证实了 CcBCL-xL 与 CcNLRP1 之间的相互作用。同时，我们还通过ASC寡聚化、ASC斑点形成和细胞毒性实验发现，CcBCL-xL能显著抑制CcNLRP1炎性体的组装。此外，我们的研究结果表明，CcBCL-xL 与 CcNLRP1 的 NACHT、LRR、FIIND 和 CARD 结构域相互作用。综上所述，这些结果为进一步探索 NLRP1 的调控机制以及预防和治疗鱼类感染性疾病提供了理论基础。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Fish & shellfish immunology 农林科学-海洋与淡水生物学

CiteScore

7.50

自引率

19.10%

发文量

750

审稿时长

68 days

期刊介绍： Fish and Shellfish Immunology rapidly publishes high-quality, peer-refereed contributions in the expanding fields of fish and shellfish immunology. It presents studies on the basic mechanisms of both the specific and non-specific defense systems, the cells, tissues, and humoral factors involved, their dependence on environmental and intrinsic factors, response to pathogens, response to vaccination, and applied studies on the development of specific vaccines for use in the aquaculture industry.