Cytokine responses induced by Toxoplasma gondii in astrocytes and microglial cells
Cytokine responses induced by Toxoplasma gondii in astrocytes and microglial cells
复制标题
DOI：
10.1002/eji.1830270633
复制
发表时间：
1997-06-01
影响因子：
5.4
通讯作者：
Hadding, U
中科院分区：
文献类型：
--
作者：
Fischer, HG;Nitzgen, B;Hadding, U
为探讨星形胶质细胞在弓形虫脑内免疫应答中的作用，将小鼠脑内培养的星形胶质细胞接种小鼠强毒株和非强毒株。与小胶质细胞/脑巨噬细胞相比，星形胶质细胞作为宿主细胞允许无毒寄生虫更强的增殖。弓形虫感染星形胶质细胞伴随着IL-1α、IL-6和粒细胞/巨噬细胞集落刺激因子(GM-CSF)活性的释放，而脂多糖(LPS)交替攻击不引起IL-1反应，并在mRNA水平上显著增加IL-6和GMCSF的滴度，两种刺激均可诱导星形胶质细胞中三种细胞因子的转录。弓形虫感染后IL-1和IL-6的分泌是由弓形虫和速殖子以时间和剂量依赖的方式触发的。热杀灭寄生虫，而不是暴露在多粘菌素B下，取消了它们的细胞因子诱导活性，因此表明弓形虫提供了一种不依赖于内毒素的刺激。当联合给药时，内毒素协同增强了弓形虫感染的IL-1诱导效应。相比之下，弓形虫诱导而不是内毒素触发的星形胶质细胞的IL-6反应抵抗IL-10的抗凝作用。外源性肿瘤坏死因子-α和转化生长因子-β(1)可上调寄生星形胶质细胞的IL-6反应，且只有肿瘤坏死因子-α能促进IL-1的同时释放。在弓形虫感染的小胶质细胞中检测到大量分泌IL-10和TNF-α，而在星形胶质细胞培养中未检测到。由于IL-1受体拮抗剂的加入不影响IL-6和GM-CSF的释放，同时抑制IL-1处理的细胞的这些反应，因此不太可能通过IL-1对感染的星形胶质细胞进行自分泌刺激。这些发现证实了弓形虫诱导的星形胶质细胞激活的一条独立的途径，其特征是释放IL-1，这可能在最初的脑感染和重新激活弓形虫期间驱动局部炎症反应。
To investigate the role of astroglia in intracerebral immune response to Toxoplasma gondii, astrocytes cultured from mouse brain were inoculated with mouse-virulent or -avirulent toxoplasma strains. In comparison to microglia/brain macrophages, astrocytes as host cells allowed stronger proliferation of avirulent parasites. Toxoplasma infection of astroglia was accompanied by release of interleukin- (IL)1 alpha, IL-6, and granulocyte/macrophage colony-stimulating factor (GM-CSF) activity, whereas alternative challenge by lipopolysaccharide (LPS) evoked no IL-1 response and significantly higher titers of IL-6 and GMCSF At the mRNA level, both stimuli induced transcription of all three cytokines in astrocytes. Secretion of IL-1 and IL-6 upon infection was triggered by T. gondii brady- and tachyzoites in a time- and dose-dependent manner. Heat killing of parasites, but not an exposure to polymyxin B, abrogated their cytokine-inducing activity, thus indicating that an LPS-independent stimulus is provided by T. gondii. When administered in combination, LPS synergistically augmented the IL-1-inducing effect of toxoplasma infection. In comparison, T. gondii-induced, but not an LPS-triggered, IL-6 response of astrocytes resisted to antagonization with IL-10. The IL-6 response of parasitized astroglia was upregulated by external tumor necrosis factor (TNF)-alpha and transforming growth factor (TGF)-beta(1), with only TNF-alpha enhancing simultaneous release of IL-1. Substantial secretion of IL-10 and TNF-alpha was detected in T. gondii-infected microglia, but not in astrocyte cultures. A possibly autocrine stimulation of infected astroglia via IL-1 was found to be unlikely, since addition of IL-1 receptor antagonist did not affect the release of IL-6 and GM-CSF while inhibiting these responses in IL-1-treated cells. The findings substantiate a separate, T. gondii-induced pathway of astroglia activation characterized by the release of IL-1 which may drive local inflammatory reaction both at initial infection of the brain and during reactivating toxoplasmosis.