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Updated: Jun 26, 2025

Polysome Profiling in Leishmania, Human Cells and Mouse Testis

Polysome Profiling in Leishmania, Human Cells and Mouse Testis

Published on: April 8, 2018

转录学分析突出了感染病毒内共生体LRV1的Leishmania braziliensis人类病变的潜在途径

Kátia Paula Felipin^1,2, Mauro Valentino Paloschi², Milena Daniela Souza Silva²

¹Laboratório de Epidemiologia Genética, Fundação Oswaldo Cruz, FIOCRUZ Rondônia, Porto Velho, Brazil.

PLoS neglected tropical diseases

|May 14, 2024

概括

莱什马尼亚RNA病毒1 (LRV1) 内生生物显著改变了宿主免疫反应在体莱什马尼亚病 (TL). 这项研究揭示了LRV1激活特定的基因通路,包括OAS/RNase L,影响疾病的严重程度.

科学领域:

免疫学免疫学免疫学
寄生虫学的寄生虫学
分子生物学分子生物学

背景情况:

体莱什曼病 (TL) 发病过程涉及复杂的宿主-寄生虫相互作用,莱什曼病 (Viannia) braziliensis是巴西的主要致病剂.
莱什马尼亚RNA病毒1 (LRV1) 在L. braziliensis中的存在与更严重的TL形式有关,如粘膜层莱什马尼亚症 (ML),但潜在的机制尚不清楚.
巨细胞在莱什马尼亚感染中至关重要,它们调解寄生虫清除和抗原呈现,影响疾病的结果.

研究的目的:

调查感染LRV1-阳性 (LbLRV1+) 与LRV1-阴性 (LbLRV1-) L. braziliensis的人类巨细胞中的分子模式和基因表达特征.
阐明LRV1在调节宿主免疫反应中的作用及其对TL病原发生的影响.
为了确定在Leishmania感染期间由LRV1的存在激活的特定信号通路.

主要方法:

使用微阵列分析在体外感染LbLRV1+和LbLRV1-菌株的人类单细胞衍生巨细胞中进行基因表达特征分析.
使用RT-qPCR验证关键的差异表达基因,特别是与I型干扰素 (IFNI) 和OAS/RNase L通路相关的基因.
通过细胞计数珠阵列 (CBA) 和ELISA分析Th1/Th2/Th17细胞因子概况.

主要成果:

微阵列分析确定了LbLRV1+和LbLRV1-感染的巨细胞之间的162个差异表达基因,其中126个与IFNI信号传递,OAS/RNAse L和维生素D3通路相关的升调基因.
RT-qPCR验证证实了与IFNI介导的途径相关的差异性基因表达,与LbLRV1+和对照细胞相比,LbLRV1+感染的细胞表达过度.
两组之间没有观察到Th1/Th2/Th17细胞因子水平的显著差异,这表明LRV1的主要影响是在基因信号水平,而不是系统性细胞因子释放.

结论:

这项研究首次证明了OAS/RNase L信号通路的激活和维生素D3在感染LRV1阳性Leishmania的巨细胞中的非基因组作用.
这些发现凸显了LRV1在指导宿主的免疫反应方面的重要作用,可能导致更严重的TL表型.
在TL患者中识别LRV1对于评估疾病进展和了解个体对感染的免疫反应至关重要.

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