弓形虫TCTP介导宿主炎性反应的分子机制研究

Toxoplasmosis is an important transmissible parasitic disease between human and animal. The pathology of Toxoplasma acute infection is associated with excess production of inflammatory mediators, signifying that the disease is due to excessive inflammatory immune responses. Excessive inflammatory immune responses led to a series of serious pathological changes and promote the development of the disease. The translationally controlled tumour protein (TCTP), also called histamine-releasing factor, is a class of highly conserved proteins. Plasmodium falciparum TCTP (PfTCTP) can stimulate the host basophils and mast cells to release histamine, and that promotes the pathological changes and the inflammatory response. T. gondii TCTP (TgTCTP) and PfTCTP are highly homologous protein. But so far there is no report about the TgTCTP. This laboratory has performed an initiatory identification for the TgTCTP. The specific fluorescence stained by anti-TgTCTP polyclonal mouse antibodies under confocal laser scanning microscopy indicated the localization of TgTCTP in the cytoplasm of T. gondii. TgTCTP could be secreted to the outside of the parasites. TgTCTP knockout parasites display invasion and growth inhibition in vitro. In this project, the pathogenicity of knockout parasites, the histamine-release activity and the active domain of TgTCTP, and the mediated effects in host inflammatory reactions will be explored on the basis of previous works.

弓形虫病是一种重要的人畜共患寄生虫病，弓形虫的严重感染往往伴随着过量炎性介质的产生，过度的炎性免疫反应导致了一系列严重的病理变化，促进了疾病的发生。翻译控制肿瘤蛋白（TCTP）又叫组胺释放因子，是一类高度保守的蛋白。疟原虫TCTP能够刺激宿主嗜碱性粒细胞和肥大细胞释放组胺，从而促进炎性反应的发生和疾病的恶化。弓形虫TCTP（TgTCTP）与疟原虫TCTP具有高度的同源性，但目前为止并未见到有关弓形虫TCTP的文献报道，本研究室已经对TgTCTP进行了初步鉴定，证明TgTCTP定位于速殖子的胞浆内并且能够分泌到虫体外侧，通过基因敲除的方法证明TgTCTP的缺失导致虫体侵入和复制受到了明显的抑制，本项目将在前期工作的基础上验证TgTCTP的缺失对于弓形虫致病性的影响，同时检测TgTCTP在体外和体内的组胺释放活性，分析TgTCTP的功能区域，探讨TgTCTP介导宿主炎性反应的分子机制。