山东大学王金星教授课题组PLOS Pathog发表对虾免疫研究成果
清道夫受体(Scavenger receptors)是一类重要的模式识别受体,在宿主对抗病原体的防御中发挥着重要的作用。C类清道夫受体(SRCs)只在一些无脊椎动物中被鉴定过,它们在对抗病毒的免疫反应中所起的作用,我们仍然知之甚少。近日,来自山东大学生命科学学院的研究人员,首次确定了来自日本对虾(Marsupenaeus japonicus)的一个SRC,命名为MjSRC。相关研究结果发表在国际期刊《pLOS pathogens》。这项研究的通讯作者是山东大学生命科学学院王金星教授。延伸阅读:山东大学JBC:一个C-型凝集素可抑制虾血淋巴菌群;山东大学课题组虾类免疫机制研究取得新进展。
这项研究发现,用白斑综合征病毒(WSSV)感染后,在mRNA和蛋白水平上,MjSRC在白细胞中都是显著上调的。与对照组相比,在MjSRC敲除后,WSSV在对虾中的数量增加。此外,MjSRC的过度表达可通过白细胞的吞噬作用,而增强WSSV的消除。pull-down和免疫共沉淀实验表明,MjSRC和WSSV囊膜蛋白之间有相互作用。电子显微镜观察表明,胶体金标记的MjSRC胞外结构域,位于WSSV的外表面。MjSRC可形成一个三聚体,并在WSSV感染后,内化进入细胞质,并且这种内化作用在Mjβ-arrestin2敲除后受到强烈抑制。
进一步的研究发现,MJβ-arrestin2可与MjSRC的胞内结构域相互作用,并以一种网格蛋白依赖性的方式诱导WSSV的内化。WSSV与血细胞中的溶酶体共定位,在溶酶体抑制剂氯喹注射后,对虾身上的WSSV白斑数量增加。总的来说,这项研究表明,MjSRC可通过其胞外结构域识别WSSV,并引起血细胞的吞噬功能,来限制WSSV全身感染。这是首次有研究将SRC报道为一种促进病毒吞噬的模式识别受体。
(生物通:王英)
注:王金星,男,1955年5月生,博士,教授。2000年被聘为博士生导师 中国动物学会理事,中国海洋与湖沼学会理事,中国兽类学会理事,《兽类学报》编委;山东动物学会常务副理事长,山东生化与分子生物学副理事长。 1981年山东师范大学本科毕业、1984年山东大学硕士研究生毕业,留校工作,1998年获南京师范大学在职博士学位。曾分别赴日本山口大学(1992)、九州工业大学(2000)、德国奥斯纳布吕克大学(1999)和吉森大学(2002)等进行合作研究。培养的博士生有1人获山东省优秀博士论文。研究生毕业后适合从事动物学、水产科学、生化与分子生物学和生物工程等方面的教学与科研工作。
生物通推荐原文摘要:
Scavenger Receptor C Mediates phagocytosis of White Spot Syndrome Virus and Restricts Virus proliferation in Shrimp
Abstract:Scavenger receptors are an important class of pattern recognition receptors that play several important roles in host defense against pathogens. The class C scavenger receptors (SRCs) have only been identified in a few invertebrates, and their role in the immune response against viruses is seldom studied. In this study, we firstly identified an SRC from kuruma shrimp, Marsupenaeus japonicus, designated MjSRC, which was significantly upregulated after white spot syndrome virus (WSSV) challenge at the mRNA and protein levels in hemocytes. The quantity of WSSV increased in shrimp after knockdown of MjSRC, compared with the controls. Furthermore, overexpression of MjSRC led to enhanced WSSV elimination via phagocytosis by hemocytes. pull-down and co-immunoprecipitation assays demonstrated the interaction between MjSRC and the WSSV envelope protein. Electron microscopy observation indicated that the colloidal gold-labeled extracellular domain of MjSRC was located on the outer surface of WSSV. MjSRC formed a trimer and was internalized into the cytoplasm after WSSV challenge, and the internalization was strongly inhibited after knockdown of Mjβ-arrestin2. Further studies found that Mjβ-arrestin2 interacted with the intracellular domain of MjSRC and induced the internalization of WSSV in a clathrin-dependent manner. WSSV were co-localized with lysosomes in hemocytes and the WSSV quantity in shrimp increased after injection of lysosome inhibitor, chloroquine. Collectively, this study demonstrated that MjSRC recognized WSSV via its extracellular domain and invoked hemocyte phagocytosis to restrict WSSV systemic infection. This is the first study to report an SRC as a pattern recognition receptor promoting phagocytosis of a virus.