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首页> 外文期刊>Infection and immunity >Cytolysin-Dependent Escape of the Bacterium from the Phagosome Is Required but Not Sufficient for Induction of the Th1 Immune Response against Listeria monocytogenes Infection: Distinct Role of Listeriolysin O Determined by Cytolysin Gene Replacement
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Cytolysin-Dependent Escape of the Bacterium from the Phagosome Is Required but Not Sufficient for Induction of the Th1 Immune Response against Listeria monocytogenes Infection: Distinct Role of Listeriolysin O Determined by Cytolysin Gene Replacement

机译：从吞噬细胞中依赖溶菌素的细菌逃逸是必需的，但不足以诱导针对单核细胞增生性李斯特菌感染的Th1免疫反应：通过溶菌素基因置换确定李斯特菌溶素O的不同作用

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Listeria monocytogenes evades the antimicrobial mechanisms of macrophages by escaping from the phagosome into the cytosolic space via a unique cytolysin that targets the phagosomal membrane, listeriolysin O (LLO), encoded by hly. Gamma interferon (IFN-γ), which is known to play a pivotal role in the induction of Th1-dependent protective immunity in mice, appears to be produced, depending on the bacterial virulence factor. To determine whether the LLO molecule (the major virulence factor of L. monocytogenes) is indispensable or the escape of bacteria from the phagosome is sufficient to induce IFN-γ production, we first constructed an hly-deleted mutant of L. monocytogenes and then established isogenic L. monocytogenes mutants expressing LLO or ivanolysin O (ILO), encoded by ilo from Listeria ivanovii. LLO-expressing L. monocytogenes was highly capable of inducing IFN-γ production and Listeria-specific protective immunity, while the hly-deleted mutant was not. In contrast, the level of IFN-γ induced by ILO-expressing L. monocytogenes was significantly lower both in vitro and in vivo, despite the ability of this strain to escape the phagosome and the intracellular multiplication at a level equivalent to that of LLO-expressing L. monocytogenes. Only a negligible level of protective immunity was induced in mice against challenge with LLO- and ILO-expressing L. monocytogenes. These results clearly show that escape of the bacterium from the phagosome is a prerequisite but is not sufficient for the IFN-γ-dependent Th1 response against L. monocytogenes, and some distinct molecular nature of LLO is indispensable for the final induction of IFN-γ that is essentially required to generate a Th1-dependent immune response.
机译：单核细胞增生性李斯特菌通过独特的溶细胞素从吞噬体逸出进入噬菌体空间，从而逃避巨噬细胞的抗菌机制，溶细胞素靶向由 hly 编码的吞噬体膜利斯特氏菌溶血素O（LLO）。 。已知会产生γ-干扰素（IFN-γ），这在小鼠中诱导Th1依赖性保护性免疫中起关键作用，具体取决于细菌的致病因子。为了确定LLO分子（单核细胞增生李斯特氏菌的主要毒力因子）是否必不可少还是细菌从吞噬体中逃逸足以诱导IFN-γ的产生，我们首先构建了一个 hly 删除的 L突变体。单核细胞增生，然后建立等基因的 L。表达LLO或伊维诺溶素O（ILO）的单核细胞增生突变体，由伊瓦斯特氏菌的 ilo 编码。表示LLO的 L。单核细胞增生因子具有很高的诱导IFN-γ产生和李斯特菌特异的保护性免疫的能力，而 hly 缺失的突变体则没有。相反，由表达ILO的 L诱导的IFN-γ水平。尽管该菌株能够以与表达LLO的 L相同的水平逃避吞噬体和细胞内增殖，但在体外和体内均显着降低了单核细胞增生因子。单核细胞增生。在小鼠中，针对表达LLO和ILO的 L激发的保护性免疫仅可忽略不计。单核细胞增生。这些结果清楚地表明，细菌从吞噬体中逃逸是先决条件，但不足以抵抗IFN-γ依赖性的Th1对Lem的应答。单核细胞增生因子和LLO的某些独特分子性质对于最终诱导IFN-γ必不可少，而IFN-γ的产生是产生Th1依赖性免疫反应所必需的。

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