Kikumura Akitoshi, Fang Hao, Mun Hye-Seong, Uemura Noriko, Makino Masayuki, Sayama Yusuke, Norose Kazumi, Aosai Fumie
Department of Infection and Host Defense, Chiba University Graduate School of Medicine, Inohana Chuo-ku, Chiba, Japan.
Parasitol Int. 2010 Jun;59(2):105-11. doi: 10.1016/j.parint.2010.03.006. Epub 2010 Mar 24.
Toxoplasma gondii-derived heat shock protein 70 (T.g.HSP70) was proven to induce lethal anaphylactic reaction in T. gondii-infected mice through platelet-activating factor (PAF)-mediated, but not classical IgE-dependent, pathway via TLR4/MyD88 signal pathway. The effector cells generating PAF and causing T.g.HSP70-induced anaphylactic reaction were CD11b(+) and CD11c(+) cells, although the reaction was enhanced by marked IFN-gamma production by CD11b(+), CD11c(+), CD4(+) and CD8(+) splenocytes. In the present study, the effects of T.g.HSP70 gene vaccine targeting peripheral dendritic cells were evaluated against T.g.HSP70-induced anaphylactic reaction in T. gondii-infected mice. C57BL/6 mice receiving T.g.HSP70 gene vaccine showed prolonged survival. Platelets of peripheral blood, which completely disappeared during the T.g.HSP70-induced anaphylactic reaction, were partially restored with the T.g.HSP70 gene vaccination. The T.g.HSP70-induced marked production of PAF and IFN-gamma from splenocytes of infected mice during the T.g.HSP70-induced anaphylactic reaction was shown to decrease after the T.g.HSP70 gene vaccination. Thus, T.g.HSP70 gene vaccine induced protective immunity against T.g.HSP70-induced PAF-mediated lethal anaphylactic reaction in T. gondii-infected mice.
弓形虫来源的热休克蛋白70(T.g.HSP70)已被证明可通过血小板活化因子(PAF)介导而非经典的IgE依赖途径,经由TLR4/MyD88信号通路,在感染弓形虫的小鼠中诱导致死性过敏反应。产生PAF并引发T.g.HSP70诱导的过敏反应的效应细胞是CD11b(+)和CD11c(+)细胞,尽管CD11b(+)、CD11c(+)、CD4(+)和CD8(+)脾细胞产生的显著干扰素-γ可增强该反应。在本研究中,评估了靶向外周树突状细胞的T.g.HSP70基因疫苗对感染弓形虫的小鼠中T.g.HSP70诱导的过敏反应的影响。接受T.g.HSP70基因疫苗的C57BL/6小鼠存活时间延长。外周血血小板在T.g.HSP70诱导的过敏反应期间完全消失,而通过T.g.HSP70基因疫苗接种可部分恢复。在T.g.HSP70诱导的过敏反应期间,感染小鼠脾细胞中T.g.HSP70诱导的显著PAF和干扰素-γ产生在T.g.HSP70基因疫苗接种后有所下降。因此,T.g.HSP70基因疫苗在感染弓形虫的小鼠中诱导了针对T.g.HSP70诱导的PAF介导的致死性过敏反应的保护性免疫。