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首页> 外文期刊>Infection and immunity >Leishmania Priming of Human Dendritic Cells for CD40 Ligand-Induced Interleukin-12p70 Secretion Is Strain and Species Dependent
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Leishmania Priming of Human Dendritic Cells for CD40 Ligand-Induced Interleukin-12p70 Secretion Is Strain and Species Dependent

机译：CD40配体诱导白细胞介素12p70分泌的人类树突状细胞的利什曼原虫引发是应变和物种依赖。

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A major question in the study of leishmaniasis is what dictates clinical disease expression produced by different Leishmania species, i.e., cutaneous versus systemic and healing versus nonhealing. Animal models using a Leishmania species associated with self-limiting cutaneous disease (L. major) have revealed that protective immunity requires CD40/CD40 ligand (CD40L)-dependent, interleukin-12 (IL-12)-driven Th1 responses. We recently showed that L. major can prime human dendritic cells (DCs) for CD40L-triggered IL-12p70 secretion and that these cells can drive a Th1 response in autologous T cells from sensitized individuals. Here we show that in contrast to L. major, Leishmania species responsible for visceral disease (L. donovani), as well as species associated with persistent, cutaneous lesions and occasional systemic disease (L. tropica), did not induce CD40L-dependent IL-12p70 production, despite comparable levels of uptake by DCs. Up-regulated surface expression of CD40 did not correlate with IL-12p70 production, and appreciable CD40L-induced IL-12p40 secretion was observed in uninfected as well as infected DCs, regardless of species. Reverse transcription-PCR analysis confirmed that the production of heterodimeric IL-12 was limited by expression of IL-12p35 mRNA, which was dependent on both a microbial priming signal and CD40 engagement for its high-level induction. The intrinsic differences in the ability of Leishmania species to prime DCs for CD40L-dependent IL-12p70 secretion may account, at least in part, for the evolution of healing and nonhealing forms of leishmanial disease.
机译：利什曼病研究中的一个主要问题是，什么决定了由不同种类的利什曼原虫产生的临床疾病表达，即皮肤与全身性疾病，愈合与非愈合性疾病。使用与自限性皮肤病（ L。major）相关的利什曼原虫物种的动物模型显示，保护性免疫需要依赖CD40 / CD40配体（CD40L）的白介素- 12（IL-12）驱动的Th1反应。我们最近显示了 L。可以使人类树突状细胞（DC）引发CD40L触发的IL-12p70分泌，并且这些细胞可以驱动致敏个体的自体T细胞中的Th1反应。在这里，我们证明了与 L相反。主要，利什曼原虫物种负责内脏疾病（ L。donovani ），以及与持续性，皮肤病变和偶发性系统疾病相关的物种（尽管DC的摄取水平相当，但L.tropica ）并未诱导CD40L依赖性IL-12p70的产生。 CD40的表面表达上调与IL-12p70的产生不相关，并且在未感染和感染的DC中观察到明显的CD40L诱导的IL-12p40分泌，而与物种无关。逆转录-PCR分析证实，异源二聚体IL-12的产生受到IL-12p35 mRNA表达的限制，IL-12p35 mRNA的表达依赖于微生物启动信号和CD40的参与。利什曼原虫物种对CD40L依赖的IL-12p70分泌引发DC的能力的内在差异可能至少部分地解释了利什曼病的愈合形式和非愈合形式。

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