Toxoplasma gondii Cyclophilin 18-Mediated Production of Nitric Oxide Induces Bradyzoite Conversion in a CCR5-Dependent Manner
Toxoplasma gondii Cyclophilin 18-Mediated Production of Nitric Oxide Induces Bradyzoite Conversion in a CCR5-Dependent Manner
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DOI：
10.1128/iai.00361-09
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发表时间：
2009-09-01
影响因子：
3.1
通讯作者：
Nishikawa, Yoshifumi
中科院分区：
文献类型：
--
作者：
Ibrahim, Hany M.;Bannai, Hiroshi;Nishikawa, Yoshifumi
刚地弓形虫通过调节促炎和抗炎反应来调节寄生虫的增殖和宿主的存活。来自免疫反应的压力导致速殖子转化为缓慢分裂的慢殖子。人们对这种转变所涉及的调控机制知之甚少。本研究的目的是研究弓形虫亲环蛋白18 （TgCyp18）在巨噬细胞中的免疫调节作用以及细胞反应对转化机制的影响。重组TgCyp18通过与半胱氨酸-半胱氨酸趋化因子受体5 （CCR5）结合诱导一氧化氮（NO）、白细胞介素-12 （IL-12）和肿瘤坏死因子α的产生，并以不依赖CCR5的方式产生γ干扰素和IL-6。有趣的是，用TgCyp18处理巨噬细胞导致寄生虫生长受到抑制，并以ccr5依赖的方式通过NO增强向慢殖子的转化。总之，弓形虫在tgcyp18介导的过程中具有复杂的机制来操纵宿主细胞的反应。
Toxoplasma gondii modulates pro- and anti-inflammatory responses to regulate parasite multiplication and host survival. Pressure from the immune response causes the conversion of tachyzoites into slowly dividing bradyzoites. The regulatory mechanisms involved in this switch are poorly understood. The aim of this study was to investigate the immunomodulatory role of T. gondii cyclophilin 18 (TgCyp18) in macrophages and the consequences of the cellular responses on the conversion machinery. Recombinant TgCyp18 induced the production of nitric oxide ( NO), interleukin-12 (IL-12), and tumor necrosis factor alpha through its binding with cysteine-cysteine chemokine receptor 5 (CCR5) and the production of gamma interferon and IL-6 in a CCR5-independent manner. Interestingly, the treatment of macrophages with TgCyp18 resulted in the inhibition of parasite growth and an enhancement of the conversion into bradyzoites via NO in a CCR5-dependent manner. In conclusion, T. gondii possesses sophisticated mechanisms to manipulate host cell responses in a TgCyp18-mediated process.