Dietary cholesterol modulates pathogen blocking by Wolbachia.
Dietary cholesterol modulates pathogen blocking by Wolbachia.
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DOI：
10.1371/journal.ppat.1003459
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发表时间：
2013
期刊：
影响因子：
6.7
通讯作者：
McGraw EA
中科院分区：
文献类型：
--
作者：
Caragata EP;Rancès E;Hedges LM;Gofton AW;Johnson KN;O'Neill SL;McGraw EA
细菌内共生体Wolbachia pipientis通过限制它们在昆虫内部形成感染的能力来保护其宿主免受一系列病原体的侵害。这种“病原体阻断”可以通过共生体的先天免疫启动、病原体和沃尔巴克氏体之间对宿主来源的资源的竞争或沃尔巴克氏体对细胞或细胞环境的直接修饰来解释。最近在果蝇和埃及伊蚊中的比较研究表明，病原体阻断不需要免疫反应，这意味着该机制必须有额外的组成部分。在这里，我们已经研究了参与的胆固醇在病原体阻断使用系统的饮食操作在果蝇结合果蝇C病毒（DCV），一种常见的苍蝇病原体的挑战。我们观察到，在富含胆固醇的饮食中感染沃尔巴克氏体菌株wMelPop和wMelCS的果蝇表现出减少的病原体阻断，病毒诱导的死亡率比在标准饮食中饲养的果蝇早2-5天发生。在胆固醇存在下，这种向更大毒力的转变也对应于宿主中更高的病毒拷贝数。有趣的是，除了一种情况外，饮食胆固醇的增加对沃尔巴克氏体密度没有影响，但这并不直接影响病原体阻断的强度。我们的研究结果表明，宿主胆固醇水平与沃尔巴克氏体感染的苍蝇抵抗DCV感染的能力有关，这表明胆固醇有助于病原体阻断的潜在机制。 Wolbachia pipientis是一种细胞内细菌，自然感染许多昆虫物种。这些细菌可以阻止多种病原体的复制和传播，这些病原体共同感染昆虫。在蚊子中，这种效应适用于包括登革热和导致疟疾的寄生虫在内的病毒。这使得沃尔巴克氏体成为一种很有前途的控制人类多种昆虫传播疾病的方法。一些研究表明，病原体阻断是由于沃尔巴克氏体刺激宿主的先天免疫系统，然而在果蝇中，阻断发生在没有这种免疫效应的情况下。这表明该机制还有一个额外的组成部分。宿主营养素如胆固醇是病毒复制的限制因素，并可能作为病原体阻断的竞争来源。在这里，我们表明，对胆固醇的竞争有助于病原体阻断作用，较高的胆固醇水平导致阻断效果较差，并增加了感染沃尔巴克氏体的D。用致病性果蝇C病毒攻击黑腹果蝇。这些结果表明，竞争胆固醇是病原体阻断机制的重要组成部分。
The bacterial endosymbiont Wolbachia pipientis protects its hosts from a range of pathogens by limiting their ability to form infections inside the insect. This “pathogen blocking” could be explained by innate immune priming by the symbiont, competition for host-derived resources between pathogens and Wolbachia, or the direct modification of the cell or cellular environment by Wolbachia. Recent comparative work in Drosophila and the mosquito Aedes aegypti has shown that an immune response is not required for pathogen blocking, implying that there must be an additional component to the mechanism. Here we have examined the involvement of cholesterol in pathogen blocking using a system of dietary manipulation in Drosophila melanogaster in combination with challenge by Drosophila C virus (DCV), a common fly pathogen. We observed that flies reared on cholesterol-enriched diets infected with the Wolbachia strains wMelPop and wMelCS exhibited reduced pathogen blocking, with viral-induced mortality occurring 2–5 days earlier than flies reared on Standard diet. This shift toward greater virulence in the presence of cholesterol also corresponded to higher viral copy numbers in the host. Interestingly, an increase in dietary cholesterol did not have an effect on Wolbachia density except in one case, but this did not directly affect the strength of pathogen blocking. Our results indicate that host cholesterol levels are involved with the ability of Wolbachia-infected flies to resist DCV infections, suggesting that cholesterol contributes to the underlying mechanism of pathogen blocking. Wolbachia pipientis is an intracellular bacterium that naturally infects many insect species. These bacteria can block the replication and dissemination of a variety of pathogens that coinfect the insect. In mosquitoes this effect applies to viruses including dengue and the parasite that causes malaria. This makes Wolbachia a promising method of controlling a number of insect-transmitted diseases of humans. Some studies suggest that pathogen blocking is due to Wolbachia stimulating the host innate immune system, however in the fly Drosophila melanogaster, blocking occurs in the absence of such an immune effect. This suggests that there is an additional component to the mechanism. Host nutrients such as cholesterol are a limiting factor in virus replication and may serve as a source of competition that underlies pathogen blocking. Here we show that competition over cholesterol contributes to the pathogen blocking effect, with higher available cholesterol levels causing less effective blocking, and increased viral titres in Wolbachia-infected D. melanogaster challenged with the pathogenic Drosophila C virus. These results suggest that competition over cholesterol is an important part of the pathogen blocking mechanism.
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