疟疾是由疟原虫感染而引起的恶性传染性疾病，对社会危害极大。天然免疫系统能识别疟原虫，进而引起相关信号通路来激活免疫系统来清除感染。目前还没有疫苗对疟疾进行有效防治，研究疟原虫相关天然免疫信号传递，揭示疟原虫感染过程中的炎症反应对于宿主防御和疟疾发生的调控成为研究热点。ELF4作为转录因子在造血细胞发育过程中发挥重要作用，申请人前期工作中发现ELF4能够调节天然免疫。ELF4缺失之后，小鼠不能够有效地控制疟原虫的复制，表现更加严重的贫血症状，Ifnαr-/-小鼠表现出相反的表型。并且发现细胞核内蛋白激酶HIPK2同ELF4相互作用，而其调节机制未知。本项目将重点研究：天然免疫转录因子ELF4在转录水平对疟原虫感染的应答和免疫调节；HIPK2如何调控ELF4疟原虫相关天然免疫信号功能；ELF4在感染条件下对血细胞生成的调控；转录相关表观遗传小分子对天然免疫以及抗疟原虫免疫反应的调节。

Malaria is a major health threat of the world caused by plasmodium infection. A series of innate immune receptors can recognize the invading plasmodium，then initiate the immune responses to eliminate the pathogens. By far the vaccine is not available yet to protect human from infection of plasmodium. The innate immunity opens up a new way to solve this difficult problem in the world. It is known that ELF4 is a regulator of hematopoiesis. We here investigated the role of ELF4 in innate immunity. Our preliminary results have shown Elf4-/- mice were much more susceptible to plasmodium infection than wild type mice, and showed more severe anemia. ELF4 is known as a type I IFN transcription factor. However, Ifn αr-/- mice were more resistant to plasmodium infection than wild type mice. We also identified that HIPK2 was able to interact with ELF4.Therefore, in this project, we are going to study: (1) The mechanism how were the cytokines and immune responses regulated by ELF4 after plasmodium infection; (2) What is the role of HIPK2 in ELF4 related anti-plasmodium innate immunity;(3) The regulatory mechanism of ELF4 mediated hematopoiesis during plasmodium infection;(4) To screen and investigate the role of epigenetic compounds in anti-plasmodium responses.