Comparison of biological functions of glycosylphosphatidylinositols from a virulent and a non virulent strain of Toxoplasma gondii

刚地弓形虫的急性感染导致产生高水平的促炎细胞因子，如IL-12和TNFa。反过来，这些细胞因子启动IFN-g的产生和各种效应机制，负责控制弓形虫感染期间寄生虫的生长和病理。然而，关于弓形虫激活先天免疫细胞并启动这种早期促炎细胞因子合成的机制，我们知之甚少。toll样受体（TLRs）是先天免疫系统识别和快速响应微生物存在的主要手段。迄今为止，tlr已涉及所有已知的引起人类疾病的微生物类别。我们最近的研究表明，刚地弓形虫速殖子中的糖基磷脂酰肌醇（GPI）锚定物在巨噬细胞启动TNFa合成中起重要作用。我们假设tlr是触发信号级联反应的中枢介质，这些信号级联反应将导致暴露于弓形虫衍生的GPI锚定的先天免疫细胞合成促炎细胞因子。我们建议开始对转染了特定TLR的细胞进行仔细的评估，以鉴定由弓形虫衍生的高纯度和合成GPI锚点激活的TLR或TLR。弓形虫的鞘脂似乎调节了gpi的炎症作用。事实上，我们的初步结果表明，其中一些抑制gpi诱导的TNFa的产生。下一步研究的目的是阐明它们的结构和功能。

Acute infection with Toxoplasma gondii results in the production of high levels of pro-inflammatory cytokines, such as IL-12 and TNFa. In turn, these cytokines initiate the production of IFN-g and various effector mechanisms that are responsible for the control of parasite growth and pathology during infection with T. gondii. However, little ist known about the mechanism by which T. gondii activates cells from innate immunity and initiates this early synthesis of pro-inflammatory cytokines. Toll-like receptors (TLRs) are the primary means the innate immune system has for recognizing and rapidly responding to the presence of microbes. To date, TLRs have been implicated in every known category of microorganisms that causes human diseases. Our recent study suggests that glycosylphosphatidylinositol (GPI) anchors from T. gondii tachyzoites have an important role in initiating the synthesis of TNFa by macrophages. We hypothesize that TLRs are central mediators in triggering signalling cascades that will lead to the synthesis of proinflammatory cytokines by cells from innate immunity exposed to GPI anchors derived from T. gondii. We propose to begin a careful evaluation of cells transfected with specific TLRs, in order to identify the TLR or TLRs activated by highly purified and synthetic GPI anchors derived from T. gondii. Sphingolipids of T. gondii seem to regulate the inflammmatory effects of the GPIs. Indeed, our preliminary results show that some of them inhibit the GPI-induced TNFa production. The aim of the next studies is to elucidate their structures and functions.