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首页> 外文期刊>Infection and immunity >Induction of unresponsiveness to gamma interferon in macrophages infected with Mycobacterium leprae.
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Induction of unresponsiveness to gamma interferon in macrophages infected with Mycobacterium leprae.

机译:诱导对麻风分枝杆菌感染的巨噬细胞对γ干扰素无反应。

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We have previously demonstrated that Mycobacterium leprae-burdened granuloma macrophages isolated from infected nude mice are refractory to activation by gamma interferon (IFN-gamma). To explore further both the afferent and efferent functional capacity of M. leprae-infected macrophages, we examined the IFN-gamma-mediated activation of resident mouse peritoneal macrophages infected in vitro with live or dead M. leprae. When IFN-gamma was administered within 24 h of M. leprae infection, macrophages were fully activated. However, defective activation was evident at 3 to 5 days postinfection in macrophages that were heavily burdened with viable M. leprae. This defect was evident by four parameters of activation in which IFN-gamma failed to stimulate the enhancement of microbicidal activity, cytotoxicity for tumor target cells, O2- production, and surface Ia antigen expression. The development of defective activation closely followed an increase in macrophage production of prostaglandin E2. Defective activation of M. leprae-burdened macrophages was reversible by indomethacin, and a similar block in IFN-gamma activation was observed in three of these four parameters in normal macrophages treated with exogenous prostaglandin E2. Thus, infection of mouse macrophages with M. leprae appears to restrict IFN-gamma-mediated activation at least in part by induction of inhibitory levels of prostaglandin E2.
机译:我们以前已经证明,从感染的裸鼠分离的麻风分枝杆菌负担的肉芽肿巨噬细胞难以被γ-干扰素(IFN-γ)激活。为了进一步探讨麻风支原体感染的巨噬细胞的传入和传出功能能力,我们检查了IFN-γ介导的活体外或死的麻风支原体感染的小鼠腹腔巨噬细胞的活化。当麻风杆菌感染后24小时内给予IFN-γ时,巨噬细胞被完全激活。然而,在感染后3至5天的巨噬细胞中,活跃的麻疯杆菌负担很重,活化功能明显不足。通过四个激活参数可以明显看出这一缺陷,其中IFN-γ未能刺激杀菌活性,对肿瘤靶细胞的细胞毒性,O2产生和表面Ia抗原表达的增强。缺陷激活的发展紧随前列腺素E2巨噬细胞产量的增加。吲哚美辛可逆转麻风杆菌负载的巨噬细胞的缺陷激活,并且在用外源前列腺素E2处理的正常巨噬细胞的这四个参数中的三个参数中,均观察到类似的IFN-γ激活阻滞。因此,麻风杆菌感染小鼠巨噬细胞似乎至少部分通过诱导抑制水平的前列腺素E2来限制IFN-γ介导的活化。

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