疟疾是由疟原虫感染引起的危害人类健康的全球性传染性疾病。目前，缺乏安全有效的疫苗是至今仍无法根除该疾病的主要原因之一，而其疫苗的研发工作最大的阻碍是对宿主在感染疟疾后复杂的固有免疫反应缺乏深入的了解和认识。宿主的固有免疫反应受到多种调控因子的共同作用调节，因此，进一步探索调控因子对宿主抗疟疾免疫反应的影响及其调控机制对新一代疫苗的研发具有重要的启发意义。我们前期研究揭示SOCS家族蛋白在不同疟原虫感染后的表达和功能存在差异，且SOCS1蛋白负调控宿主抗疟疾YM的免疫反应。在本项目中，我们将采用基因缺陷型动物模型和细胞模型，结合免疫学和分子生物学方法，探究SOCS家族蛋白在宿主种属特异性免疫反应中的作用，并从细胞水平探索其调控机制，最后将进一步研究SOCS调控的固有免疫信号在抗疟疾和肿瘤中的作用。我们的研究将丰富现有的固有免疫调节理论，为新一代疫苗的研发和肿瘤治疗提供新的分子靶点和理论方向。

Malaria infects over 300 million people and is responsible for up to 1 million deaths worldwide, causing it to remain a major global public health threat. The lack of effective vaccines is one of major contributing factors in controlling the disease. The difficulties in effective vaccine development against Plasmodium spp. may be due to a poor understanding of parasite interactions with host immune responses and the complicated regulation of regulators in innate immune responses. Thus, it is of vital importance to understand mechanisms of innate immune regulation in disease progression and host mortality in response to malaria infection. Our preliminary data showed strain-specific expression and function of SOCS family after various plasmodium infection, and SOCS1 negatively regulates host immune responses after YM infection. In this proposal, by combining the methods of immunology and molecular biology, we plan to investigate the function of SOCS family in strain-specific immune responses against malaria infection, as well as the mechanism and application in anti-malaria and anti-tumor progress. Our proposed study will facilitate the development of effective malaria vaccines and new target of immune therapy.