对虾NLR基因的免疫学功能及其分子调控机制研究

由模式识别受体介导的免疫识别是先天免疫反应中最为关键的过程。作为一种胞质型模式识别受体，脊椎动物NLRs在调控NF-κB等先天免疫信号通路、活化炎症小体及维持肠道稳态等过程发挥关键作用。然而，NLRs在无脊椎动物中的免疫功能仍未见报道。申请人近期从凡纳滨对虾中获得一条NLRs同源基因LvNLR，其推导氨基酸序列具有类似于哺乳动物NLRs的结构域组成。本项目拟分析LvNLR与同源基因的进化关系，研究其对不同病原或病原相关分子模式的响应和识别特征，分析其在肠道稳态中的作用，阐释该基因的免疫学功能；分析LvNLR不同结构域的功能，研究其对NF-κB、MAPK通路及炎症反应基因Caspase-1的调控作用，探索N末端结构域的互作蛋白及功能，解析该基因功能的分子调控机制。结果将填补无脊椎动物NLRs功能及节肢动物NLRs进化的研究空白，不但丰富无脊椎动物先天免疫理论认知，也为对虾病害防治提供新思路。

Immune recognition, mediated by pattern recognition receptors (PRRs), is the most important process in innate immune responses. As a kind of cytoplasmic PRRs, NOD-like receptors (NLRs) in vertebrates play key roles in the regulation of innate immune signaling pathways like NF-κB pathway, activation of inflammatory body and maintenance of intestinal homeostasis. However, the immunological function of NLRs in invertebrates is still unclear. Recently, we obtained a NLRs homologous gene (LvNLR) from the Pacific whiteleg shrimp Litopenaeus vannamei. The deduced amino acid sequence of LvNLR has a similar domain composition as mammals NLRs. In the present study, we will analyze the phylogenetic relationship of LvNLR and its homologues. We will study the responses and recognition patterns of LvNLR to different pathogens and PAMPs and the function of LvNLR in intestinal homeostasis to interpret its immunological function. The function of different LvNLR domains will be analyzed. The regulatory effects of LvNLR on NF-κB and MAPK signaling pathway and inflammatory gene Caspase-1 will be studied. The interaction proteins the N-terminal domain and their immunological functions will be explored. These results will be used to explain the molecular regulation mechanism of the immunological function of LvNLR. The data will fill the research gap of invertebrates NLRs gene function and the evolution of arthropods NLRs. The study will not only enrich the innate immune theory of invertebrates, but also provide new insights into shrimp diseases control.