Scavenger receptor B2, a type III membrane pattern recognition receptor, senses LPS and activates the IMD pathway in crustaceans.

Scavenger receptor B2, a type III membrane pattern recognition receptor, senses LPS and activates the IMD pathway in crustaceans.
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DOI:
10.1073/pnas.2216574120
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发表时间:
2023-06-13
影响因子:
11.1
通讯作者:
Wang, Jin-Xing
Wang, Jin-Xing
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Shi, Xiu-Zhen;Yang, Ming-Chong;Kang, Xin-Le;Li, Yan-Xue;Hong, Pan-Pan;Zhao, Xiao-Fan;Vasta, Gerardo R.;Wang, Jin-Xing

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无脊椎动物完全依靠先天机制来保护免受微生物感染。在这些机制中,免疫缺陷(IMD)途径对于成功应对病原体至关重要。在黑腹果蝇中,IMD途径的典型受体是肽聚糖识别蛋白,这在甲壳类动物中是缺乏的,表明涉及甲壳类动物中先前未鉴定的机制。在这里,我们报告了一个B类清道夫受体从虾,作为一个关键的识别和IMD途径的信号受体。我们的研究还揭示了保守的途径特征,如NF-κB信号激活的淀粉样纤维的形成。此外,陆生和水生节肢动物谱系中先天免疫途径的机制分歧可能揭示进化过程中的关键环境适应。免疫缺陷(IMD)途径是提高昆虫和甲壳类动物宿主免疫力的关键。昆虫IMD通路的激活是由肽聚糖识别蛋白介导的,而肽聚糖识别蛋白在甲壳类动物中不存在,这表明甲壳类动物IMD通路激活中涉及的一种先前未鉴定的机制。在这项研究中,我们确定了一个Marsupenaeus的B类III型清道夫受体,SRB 2,作为一个受体的IMD通路的激活。SRB 2在细菌攻击后上调,而其缺失通过消除抗菌肽的表达而加剧细菌增殖和虾死亡。SRB 2的细胞外结构域识别细菌脂多糖(LPS),而其C-末端含有隐蔽的RHIM样基序的细胞内区域与IMD相互作用,并通过促进RELISH的核转位激活该途径。在果蝇S2细胞中过表达虾SRB 2增强LPS诱导的IMD通路激活和Diptericin表达。这些结果揭示了一个以前未被认识到的SRB 2-IMD轴负责抗菌肽诱导和限制甲壳类动物中的细菌感染,并提供了IMD信号在动物中的生物多样性的证据。更好地了解甲壳类动物的先天免疫将允许对所出现的虾病的预防和治疗策略的优化。
Invertebrates rely exclusively on innate mechanisms for protection against microbial infection. Among these mechanisms, the immune deficiency (IMD) pathway is critical for successful responses against pathogens. In Drosophila melanogaster, the typical receptors for the IMD pathway are peptidoglycan recognition proteins, which are lacking in crustaceans, suggesting the involvement of a previously unidentified mechanism involved in crustaceans. Here, we report a B-class scavenger receptor from shrimp that functions as a key recognition and signaling receptor for the IMD pathway. Our study also revealed conserved pathway features such as the formation of amyloid fibrils for NF-κB signaling activation. Furthermore, the mechanistic divergence of innate immunity pathways in terrestrial and aquatic arthropod lineages may reveal key environmental adaptations in the course of evolution. The immune deficiency (IMD) pathway is critical for elevating host immunity in both insects and crustaceans. The IMD pathway activation in insects is mediated by peptidoglycan recognition proteins, which do not exist in crustaceans, suggesting a previously unidentified mechanism involved in crustacean IMD pathway activation. In this study, we identified a Marsupenaeus japonicus B class type III scavenger receptor, SRB2, as a receptor for activation of the IMD pathway. SRB2 is up-regulated upon bacterial challenge, while its depletion exacerbates bacterial proliferation and shrimp mortality via abolishing the expression of antimicrobial peptides. The extracellular domain of SRB2 recognizes bacterial lipopolysaccharide (LPS), while its C-terminal intracellular region containing a cryptic RHIM-like motif interacts with IMD, and activates the pathway by promoting nuclear translocation of RELISH. Overexpressing shrimp SRB2 in Drosophila melanogaster S2 cells potentiates LPS-induced IMD pathway activation and diptericin expression. These results unveil a previously unrecognized SRB2-IMD axis responsible for antimicrobial peptide induction and restriction of bacterial infection in crustaceans and provide evidence of biological diversity of IMD signaling in animals. A better understanding of the innate immunity of crustaceans will permit the optimization of prevention and treatment strategies against the arising shrimp diseases.
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发表时间: 2016-02-09
影响因子: 16.6
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