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首页> 外文期刊>The Journal of Immunology: Official Journal of the American Association of Immunologists >IFN-beta impairs superoxide-dependent parasite killing in human macrophages: evidence for a deleterious role of SOD1 in cutaneous leishmaniasis.
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IFN-beta impairs superoxide-dependent parasite killing in human macrophages: evidence for a deleterious role of SOD1 in cutaneous leishmaniasis.

机译:干扰素-β损害人类巨噬细胞中超氧化物依赖性寄生虫的杀伤:SOD1在皮肤利什曼病中的有害作用的证据。

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摘要

Type I IFNs (IFN-alpha/beta) have only recently gained considerable attention as immunomodulators in nonviral infectious diseases. IFN-beta has been shown to protect, in a NO-dependent manner, against murine Old World leishmaniasis caused by Leishmania major, but data in New World leishmaniasis are lacking. We found that IFN-beta dose-dependently increases parasite burden in Leishmania amazonensis- as well as Leishmania braziliensis-infected human macrophages, independent of endogenous or exogenous NO. However, IFN-beta significantly reduced superoxide release in Leishmania-infected as well as uninfected human macrophages. This decrease in superoxide production was paralleled by a significant IFN-beta-mediated increase in superoxide dismutase 1 (SOD1) protein levels. Additionally, IFN-beta inhibition of leishmanicidal activity was mimicked by SOD1 and antagonized by either pharmacological or small interfering RNA-mediated inhibition of SOD1. Finally, pronounced SOD1 expression in situ was demonstrated in biopsies from New World cutaneous leishmaniasis patients. These findings reveal a hitherto unknown IFN-beta/SOD1 axis in Leishmania infection and suggest that inhibition of SOD-associated pathways could serve as strategy in the treatment of L. amazonensis as well as L. braziliensis infection, major human pathogens.
机译:作为非病毒感染性疾病的免疫调节剂,I型干扰素(IFN-alpha / beta)直到最近才引起人们的广泛关注。 IFN-β已经显示出以NO依赖性的方式保护免于由大的利什曼原虫引起的鼠旧世界利什曼病,但是缺乏新世界利什曼病的数据。我们发现,IFN-β剂量依赖性地增加了亚马逊利什曼原虫以及巴西利什曼原虫感染的人类巨噬细胞的寄生虫负担,而与内源性或外源性NO无关。但是,IFN-β显着降低了利什曼原虫感染和未感染的人类巨噬细胞中的超氧化物释放。超氧化物产量的下降与超氧化物歧化酶1(SOD1)蛋白水平的明显干扰素β介导的增加同时发生。此外,SOD1模仿了IFN-β的杀菌活性抑制作用,而药理学或小干扰RNA介导的SOD1抑制作用则与IFN-β拮抗作用。最后,在新世界皮肤利什曼病患者的活检中证实了明显的SOD1原位表达。这些发现揭示了利什曼原虫感染中迄今未知的IFN-β/ SOD1轴,并表明抑制SOD相关途径可作为治疗人的主要病原体亚马逊乳杆菌和巴西乳杆菌感染的策略。

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