Roles of IFN-γ and MyD88 on dendritic cell-vaccine with T. gondii-HSP70

弓形虫感染宿主的病理结果不仅受弓形虫毒力或致病性的差异调节，而且还受宿主的遗传保护性免疫的影响。我们曾报道过Fn-.缺陷小鼠和MyD88缺陷小鼠在7-10天内死亡。在本研究中，这些小鼠株作为免疫缺陷小鼠模型，分析了弓形虫HSP70(T.g.HS70)基因疫苗靶向外周未成熟树突状细胞(DC)的效果。首先，Fn-γ和MyD88缺陷小鼠的DC均能在T.g.HS70刺激下分化为成熟DC，并可诱导同基因未成熟WT小鼠Th1极化。其次，HS70基因疫苗能成功诱导引流淋巴结(DLN)中CD^4 T细胞的DC成熟和Th1分化，在接种后第5天达到最大。对这些事件的天然免疫分析表明，TLR4/MyD88信号通路不仅在疫苗效应的急性期参与，而且在慢性期也参与其中。

Pathological findings in Toxoplasma gondii-infected host are regulated not only by differences in virulence or pathogenecity of T. gondii strains but also by genetic protective immunity of hosts. We have reported that FN-.deficient mice and MyD88 deficient mice succumbed within 7-10days. In the present study, these murine strains are used as immune-deficient mouse models and have analyzed the effects of T. gondii-HSP70 (T.g.HS70) gene vaccine targeting peripheral immature dendritic cells (DC). Firstly, DC from both FN-γ.and MyD88 deficient mice are capable to differentiate into mature DC by the stimulation with T.g.HS70 and successively induce Th1 polarization from Th0 of syngeneic naive WT mice. Secondary, T.g.HS70 gene vaccine succeeds to induce DC maturation and successive Th1 polarization of CD^4+ T cells in the draining lymph nodes (dLN) maximal at day 5 after the vaccine. Analyses of innate immunity in these events revealed that TLR4/MyD88 signal pathway is involved not only at acute phase but also at chronic phase of vaccine effects.