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Binding of a C-type lectin’s coiled-coil domain to the Domeless receptor directly activates the JAK/STAT pathway in the shrimp immune response to bacterial infection
PLoS Pathogens ( IF 5.5 ) Pub Date : 2017-09-20 , DOI: 10.1371/journal.ppat.1006626
Jie-Jie Sun 1 , Jiang-Feng Lan 1 , Xiao-Fan Zhao 1 , Gerardo R Vasta 2 , Jin-Xing Wang 1
Affiliation  

C-type lectins (CTLs) are characterized by the presence of a C-type carbohydrate recognition domain (CTLD) that by recognizing microbial glycans, is responsible for their roles as pattern recognition receptors in the immune response to bacterial infection. In addition to the CTLD, however, some CTLs display additional domains that can carry out effector functions, such as the collagenous domain of the mannose-binding lectin. While in vertebrates, the mechanisms involved in these effector functions have been characterized in considerable detail, in invertebrates they remain poorly understood. In this study, we identified in the kuruma shrimp (Marsupenaeus japonicus) a structurally novel CTL (MjCC-CL) that in addition to the canonical CTLD, contains a coiled-coil domain (CCD) responsible for the effector functions that are key to the shrimp’s antibacterial response mediated by antimicrobial peptides (AMPs). By the use of in vitro and in vivo experimental approaches we elucidated the mechanism by which the recognition of bacterial glycans by the CTLD of MjCC-CL leads to activation of the JAK/STAT pathway via interaction of the CCD with the surface receptor Domeless, and upregulation of AMP expression. Thus, our study of the shrimp MjCC-CL revealed a striking functional difference with vertebrates, in which the JAK/STAT pathway is indirectly activated by cell death and stress signals through cytokines or growth factors. Instead, by cross-linking microbial pathogens with the cell surface receptor Domeless, a lectin directly activates the JAK/STAT pathway, which plays a central role in the shrimp antibacterial immune responses by upregulating expression of selected AMPs.



中文翻译:


C 型凝集素的卷曲螺旋结构域与 Domeless 受体的结合直接激活虾对细菌感染的免疫反应中的 JAK/STAT 通路



C 型凝集素 (CTL) 的特征是存在 C 型碳水化合物识别结构域 (CTLD),该结构域通过识别微生物聚糖,在细菌感染的免疫反应中发挥模式识别受体的作用。然而,除了 CTLD 之外,一些 CTL 还显示可以执行效应子功能的其他结构域,例如甘露糖结合凝集素的胶原结构域。虽然在脊椎动物中,涉及这些效应器功能的机制已得到相当详细的表征,但在无脊椎动物中,人们对它们仍然知之甚少。在这项研究中,我们在车虾( Marsupenaeus japonicus )中发现了一种结构新颖的 CTL (MjCC-CL),除了典型的 CTLD 之外,还包含一个卷曲螺旋结构域 (CCD),负责负责效应子功能,而效应子功能是虾的抗菌反应由抗菌肽(AMP)介导。通过使用体外体内实验方法,我们阐明了 MjCC-CL 的 CTLD 识别细菌聚糖通过CCD 与表面受体 Domeless 相互作用而激活 JAK/STAT 途径的机制,并且AMP 表达上调。因此,我们对虾 MjCC-CL 的研究揭示了与脊椎动物的显着功能差异,其中 JAK/STAT 途径通过细胞因子或生长因子被细胞死亡和应激信号间接激活。相反,通过将微生物病原体与细胞表面受体 Domeless 交联,凝集素直接激活 JAK/STAT 途径,该途径通过上调所选 AMP 的表达在虾抗菌免疫反应中发挥核心作用。

更新日期:2017-09-20
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