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首页> 外文期刊>Infection and immunity >The Down-Regulation of Cathepsin G in THP-1 Monocytes after Infection with Mycobacterium tuberculosis Is Associated with Increased Intracellular Survival of Bacilli
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The Down-Regulation of Cathepsin G in THP-1 Monocytes after Infection with Mycobacterium tuberculosis Is Associated with Increased Intracellular Survival of Bacilli

机译：结核分枝杆菌感染后THP-1单核细胞中组织蛋白酶G的下调与细菌的细胞内存活率增加有关。

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Cathepsin G (CatG) is a serine protease found in the azurophilic granules of monocytes that is known to have antimicrobial properties, but its role in Mycobacterium tuberculosis infection is unknown. We found that M. tuberculosis infection of human THP-1 monocytic cells induced the down-regulation of CatG mRNA expression, as demonstrated by gene array analysis and reverse transcription-PCR. This was associated with a concomitant decrease in CatG protein and enzymatic activity. In contrast, the expression of lysosomal cathepsins B and D was up-regulated in infected cells. This effect was also observed when THP-1 cells were induced to differentiate into adherent macrophages by exposure to bacterial lipopolysaccharide (LPS). In agreement with this, CatG expression was null in adherent macrophages isolated from bronchoalveolar lavages and normal blood. We wanted to determine if the down-regulation of CatG would be relevant to M. tuberculosis infection. First, we found that addition of CatG to THP-1 cells prior to infection resulted in decreased bacillary viability, presumably due to extracellular killing of bacilli. However, pretreatment of cells with LPS, which decreases intracellular CatG expression, resulted in increased bacillary viability. Second, we found that CatG cationic peptides killed M. tuberculosis bacilli and were five- to sevenfold more bactericidal than full-length CatG. These observations suggest that M. tuberculosis infection of human monocytic cells results in a “cathepsin switch” with down-regulation of CatG rendering M. tuberculosis bacilli more viable. Therefore, the down-regulation of CatG in macrophages is advantageous to M. tuberculosis bacilli and possibly is an important mechanism by which M. tuberculosis is able to evade the host immune defenses.
机译：组织蛋白酶G（CatG）是一种在单核细胞的嗜酸性颗粒中发现的丝氨酸蛋白酶，已知具有抗菌特性，但在结核分枝杆菌感染中的作用尚不清楚。我们发现 M。基因阵列分析和逆转录PCR结果表明，人THP-1单核细胞的结核病感染导致CatG mRNA表达下调。这与CatG蛋白和酶活性的同时降低有关。相反，溶酶体组织蛋白酶B和D的表达在被感染的细胞中被上调。当通过暴露于细菌脂多糖（LPS）诱导THP-1细胞分化为贴壁巨噬细胞时，也观察到了这种效果。与此相符的是，在从支气管肺泡灌洗液和正常血液中分离的粘附巨噬细胞中，CatG表达无效。我们想确定CatG的下调是否与 M有关。结核感染。首先，我们发现在感染前向THP-1细胞中添加CatG会导致细菌生存力下降，这大概是由于细菌的细胞外杀伤所致。但是，用LPS预处理细胞会降低细胞内CatG表达，从而导致细菌活力增加。其次，我们发现CatG阳离子肽杀死了 M。结核杆菌的杀菌能力比全长CatG高五到七倍。这些观察结果表明， M。人单核细胞的肺结核感染会导致“组织蛋白酶转换”，并下调CatG渲染 M。结核杆菌更可行。因此，巨噬细胞中CatG的下调有利于M。结核杆菌可能是 M的重要机制。结核病能够逃避宿主的免疫防御。

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