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首页> 外文期刊>Infection and immunity >Dissociated Linkage of Cytokine-Inducing Activity and Cytotoxicity to Different Domains of Listeriolysin O from Listeria monocytogenes
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Dissociated Linkage of Cytokine-Inducing Activity and Cytotoxicity to Different Domains of Listeriolysin O from Listeria monocytogenes

机译：单核细胞增生李斯特菌的细胞因子诱导活性和对李斯特菌溶血素O不同域的细胞毒性的解离联系。

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摘要

Listeriolysin O (LLO), a cholesterol-binding cytolysin of Listeria monocytogenes, exhibits cytokine-inducing and cytolytic activities. Because the cytolytic activity was abolished by cholesterol treatment but the cytokine-inducing activity was not, these activities appeared to be linked to different domains of the LLO molecule. In this study, we constructed recombinant full-length LLO (rLLO529) and various truncated derivatives and examined their cytolytic, cholesterol-binding, and gamma interferon (IFN-γ)-inducing activities. rLLO529 exhibited both IFN-γ-inducing and cytolytic activities. Four truncated rLLOs possessing different C termini, which did not exert either cytolytic or cholesterol-binding activity, stimulated IFN-γ production in normal spleen cells. However, a truncated rLLO corresponding to domain 4 (rLLO416-529) did not exhibit IFN-γ-inducing activity, whereas it did bind to immobilized cholesterol. In addition, though the hemolysis induced by rLLO529 was inhibited by rLLO416-529, such inhibition was not detected upon rLLO529-induced IFN-γ production. These data indicated that domain 4 was responsible for binding of LLO to membrane cholesterol followed by oligomerization and pore formation by the entire LLO molecule. In contrast, the other part of LLO, corresponding to domain 1-3, was essential for IFN-γ-inducing activity. These findings implied a novel aspect of the function of LLO as a bacterial modulin.
机译：李斯特菌单核细胞增生李斯特菌的胆固醇结合型溶细胞素李斯特菌溶血素O（LLO）具有诱导细胞因子和溶细胞的活性。由于胆固醇处理消除了细胞溶解活性，但没有诱导细胞因子的活性，因此这些活性似乎与LLO分子的不同结构域相关。在这项研究中，我们构建了重组全长LLO（rLLO529）和各种截短的衍生物，并检查了它们的溶细胞，胆固醇结合和γ-干扰素（IFN-γ）诱导活性。 rLLO529表现出IFN-γ诱导和细胞溶解活性。四个截短的rLLO具有不同的C末端，这些末端既不具有细胞溶解作用也不具有胆固醇结合活性，它们刺激了正常脾细胞中的IFN-γ产生。但是，对应于结构域4（rLLO416-529）的截短的rLLO不显示IFN-γ诱导活性，而与固定的胆固醇结合。另外，尽管rLLO529诱导的溶血被rLLO416-529抑制，但在rLLO529诱导的IFN-γ产生时未检测到这种抑制。这些数据表明结构域4负责LLO与膜胆固醇的结合，随后是整个LLO分子的寡聚和孔形成。相反，LLO的另一部分（对应于结构域1-3）对于IFN-γ诱导活性至关重要。这些发现暗示了LLO作为细菌调节蛋白的功能的新方面。

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