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印度鲤鱼(Cirrhinus mrigala)在配体暴露和细菌感染后 Toll 样受体 5(TLR5)及其相关下游信号分子的诱导表达。

Inductive expression of toll-like receptor 5 (TLR5) and associated downstream signaling molecules following ligand exposure and bacterial infection in the Indian major carp, mrigal (Cirrhinus mrigala).

机构信息

Fish Health Management Division, Central Institute of Freshwater Aquaculture, Kausalyaganga, Bhubaneswar, Orissa 751002, India.

出版信息

Fish Shellfish Immunol. 2012 Jan;32(1):121-31. doi: 10.1016/j.fsi.2011.10.031. Epub 2011 Nov 7.

DOI:10.1016/j.fsi.2011.10.031
PMID:22085689
Abstract

Toll-like receptors (TLRs) are one of the key components of innate immunity. Among various types of TLRs, TLR5 is involved in recognizing bacterial flagellin and after binding, it triggers myeloid differentiation primary response gene 88 (MyD88)-dependent signaling pathway to induce pro-inflammatory cytokines. In this report, we analyzed the expression profile of TLR5 and its associated downstream signaling molecules like MyD88 and tumor necrosis factor (TNF) receptor-associated factor (TRAF) 6 in the Indian major carp (IMC), mrigal (Cirrhinus mrigala) which is highly commercially important fish species in the Indian subcontinent. Ontogeny analysis of TLR5, MyD88 and TRAF6 revealed constitutive expression of these genes in all embryonic developmental stages, and highlighted the importance of embryonic innate immune defense system in fish. Tissue specific expression analysis of these genes by quantitative real-time PCR (qRT-PCR) revealed their wide distribution in various organs and tissues; highest expression of TLR5 and MyD88 was in liver and TRAF6 was in kidney. Modulation of TLR5, MyD88 and TRAF6 gene expression, and the induction of interleukin (IL)-8 and TNF-α were analyzed in various organs by qRT-PCR following flagellin stimulation, and Aeromonas hydrophila and Edwardsiella tarda infection. In the treated fish, majority of the tested tissues exhibited significant induction of these genes, although with varied intensity among the tissues and with the types of treatments. Among the examined tissues, a significant relationship of TLR5 induction, MyD88 and TRAF6 up-regulation, and enhanced expression of IL-8 and TNF-α gene transcripts was observed in the blood and intestine of both flagellin stimulated and bacteria infected fish. These findings may indicate the involvement of TLR5 in inducing IL-8 and TNF-α, and suggest the important role of TLR5 in augmenting innate immunity in fish in response to pathogenic invasion. This study will enrich the information in understanding the innate immune mechanism in fish and may be helpful in developing preventive measures against infectious diseases in fish.

摘要

Toll 样受体 (TLRs) 是先天免疫的关键组成部分之一。在各种类型的 TLR 中,TLR5 参与识别细菌鞭毛蛋白,结合后触发髓样分化初级反应基因 88 (MyD88) 依赖性信号通路,诱导促炎细胞因子。在本报告中,我们分析了印度鲤鱼 (IMC) 中 TLR5 及其相关下游信号分子,如 MyD88 和肿瘤坏死因子 (TNF) 受体相关因子 (TRAF) 6 的表达谱,印度次大陆具有重要商业价值的鱼类。TLR5、MyD88 和 TRAF6 的个体发生分析显示这些基因在所有胚胎发育阶段都有组成型表达,强调了鱼类胚胎先天免疫防御系统的重要性。通过定量实时 PCR (qRT-PCR) 进行的这些基因的组织特异性表达分析表明它们在各种器官和组织中的广泛分布; TLR5 和 MyD88 的表达最高,TRAF6 在肾脏中表达最高。鞭毛蛋白刺激和嗜水气单胞菌和爱德华氏菌感染后,通过 qRT-PCR 分析了各种器官中 TLR5、MyD88 和 TRAF6 基因表达的调节以及白细胞介素 (IL)-8 和肿瘤坏死因子 (TNF)-α 的诱导。在处理过的鱼中,大多数测试组织都表现出这些基因的显著诱导,尽管组织之间的强度不同,并且处理方式也不同。在所检查的组织中,在鞭毛蛋白刺激和细菌感染的鱼的血液和肠道中观察到 TLR5 诱导、MyD88 和 TRAF6 上调以及 IL-8 和 TNF-α 基因转录物表达增强之间存在显著关系。这些发现可能表明 TLR5 参与诱导 IL-8 和 TNF-α,并表明 TLR5 在增强鱼类对病原入侵的先天免疫方面的重要作用。本研究将丰富鱼类先天免疫机制的信息,并可能有助于开发鱼类传染病的预防措施。

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