拟穴青蟹MD2同源物介导抗弧菌免疫信号途径的识别和激活机制研究

弧菌疾病严重危害虾蟹养殖业发展，目前对甲壳动物抗弧菌免疫机制缺乏足够了解,限制了对弧菌病的防治。LPS是弧菌表面重要组分，能诱导动物的免疫应答。哺乳动物MD2能识别LPS，是激活TLR4信号途径必需蛋白。我们的前期研究证明拟穴青蟹SpToll途径参与抗弧菌反应，但识别和激活机制并不清楚。我们在青蟹中鉴定到MD2同源物SpMD2，其可结合LPS并影响弧菌对抗菌肽的诱导，推测其可能位于SpToll上游，参与该途径的识别和激活。另外，我们还发现青蟹LGBP可能结合并提呈LPS，增强上述途径的激活效果。为证实该推测，本项目拟研究LPS、SpMD2和SpToll形成复合体的可能性及互作方式，明确上述复合体是否激活信号途径而调控抗菌肽表达，探明SpLGBP提呈LPS及其增强激活信号途径的可能性。本项目预期阐明SpMD2介导的抗弧菌信号途径的特异识别和激活机制，为虾蟹弧菌疾病防治提供新的理论支撑。

Vibriosis greatly restricts the development of the aquaculture of shrimp and crabs. The lack of full knowledge about the immune mechanism against Vibrio limited the prevention and control of vibriosis. LPS is the important component on Vibrio surface, and can induce the immune response of animals. The mammalian MD2 can recognize LPS and is critical for the activation of TLR4 signaling pathway. Previous study proved that Scylla paramamosain Toll could mediate the anti-Vibrio response, but the recognition and activation mechanism is unclear. We identified a MD2 homolog (SpMD2) and found it can recognize LPS and modulate the induction of antimicrobial peptide expression by Vibrio infection. We speculate SpMD2 is located upstream of SpToll and mediates the recognition and activation of TLR Pathway. Besides, we found the mud crab LGBP might bind and present LPS, and strengthen the TLR pathway. To confirm the speculation, this program is planned to study the possibility that the formation of LPS-SpMD2-SpToll complex, to investigate whether the complex can activate the TLR pathway and regulate the antimicrobial peptide expression, and to explore whether SpLGBP can present LPS to TLR pathway to strengthen the activation. This study will illustrate the specific recognition and activation mechanism of the anti-Vibrio signaling pathway mediated by SpMD2, and provide new insights to the prevention and control of vibriosis.