Trypanosoma cruzi reprograms mitochondrial metabolism within the anterior midgut of its vector Rhodnius prolixus during the early stages of infection.

IF 3 2区 医学 Q1 PARASITOLOGY
Radouane Ouali, Larissa Rezende Vieira, Didier Salmon, Sabrina Bousbata
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引用次数: 0

Abstract

Background: Trypanosoma cruzi is transmitted to humans by hematophagous bugs belonging to the Triatominae subfamily. Its intra-vectorial cycle is complex and occurs exclusively in the insect's midgut. Dissecting the elements involved in the cross-talk between the parasite and its vector within the digestive tract should provide novel targets for interrupting the parasitic life cycle and affecting vectorial competence. These interactions are shaped by the strategies that parasites use to infect and exploit their hosts, and the host's responses that are designed to detect and eliminate parasites. The objective of the current study is to characterize the impact of T. cruzi establishment within its vector on the dynamics of its midgut.

Methods: In this study, we evaluated the impact of T. cruzi infection on protein expression within the anterior midgut of the model insect Rhodnius prolixus at 6 and 24 h post-infection (hpi) using high-throughput quantitative proteomics.

Results: Shortly after its ingestion, the parasite modulates the proteome of the digestive epithelium by upregulating 218 proteins and negatively affecting the expression of 11 proteins involved in a wide array of cellular functions, many of which are pivotal due to their instrumental roles in cellular metabolism and homeostasis. This swift response underscores the intricate manipulation of the vector's cellular machinery by the parasite. Moreover, a more in-depth analysis of proteins immediately induced by the parasite reveals a pronounced predominance of mitochondrial proteins, thereby altering the sub-proteomic landscape of this organelle. This includes various complexes of the respiratory chain involved in ATP generation. In addition to mitochondrial metabolic dysregulation, a significant number of detoxifying proteins, such as antioxidant enzymes and P450 cytochromes, were immediately induced by the parasite, highlighting a stress response.

Conclusions: This study is the first to illustrate the response of the digestive epithelium upon contact with T. cruzi, as well as the alteration of mitochondrial sub-proteome by the parasite. This manipulation of the vector's physiology is attributable to the cascade activation of a signaling pathway by the parasite. Understanding the elements of this response, as well as its triggers, could be the foundation for innovative strategies to control the transmission of American trypanosomiasis, such as the development of targeted interventions aimed at disrupting parasite proliferation and transmission within the triatomine vector.

在感染的早期阶段,克鲁斯锥虫对其载体 Rhodnius prolixus 的前中肠内的线粒体代谢进行了重编程。
背景:克鲁兹锥虫是由三足虫亚科的食血虫传播给人类的。它的载体内循环非常复杂,而且只发生在昆虫的中肠。剖析寄生虫与其载体在消化道内交叉对话所涉及的要素,将为中断寄生虫生命周期和影响载体能力提供新的目标。寄生虫感染和利用宿主的策略以及宿主检测和消灭寄生虫的反应决定了这些相互作用。本研究的目的是确定在载体内建立 T. cruzi 对其中肠道动态的影响:在这项研究中,我们利用高通量定量蛋白质组学评估了感染 T. cruzi 对模型昆虫 Rhodnius prolixus 感染后 6 小时和 24 小时(hpi)前中肠内蛋白质表达的影响:结果:寄生虫摄入后不久就会调节消化道上皮细胞的蛋白质组,上调 218 种蛋白质,并对 11 种参与多种细胞功能的蛋白质的表达产生负面影响,其中许多蛋白质在细胞新陈代谢和稳态中起着关键作用。这种快速反应凸显了寄生虫对载体细胞机制的复杂操控。此外,对寄生虫立即诱导的蛋白质进行更深入的分析后发现,线粒体蛋白质明显占优势,从而改变了这一细胞器的亚蛋白质组格局。这包括参与产生 ATP 的呼吸链的各种复合物。除了线粒体代谢失调外,寄生虫还立即诱导了大量解毒蛋白,如抗氧化酶和 P450 细胞色素,凸显了应激反应:这项研究首次说明了消化道上皮细胞在接触克柔蚊后的反应,以及寄生虫对线粒体亚蛋白质组的改变。这种对载体生理机能的操纵可归因于寄生虫对信号通路的级联激活。了解这种反应的要素及其触发因素,可以为控制美洲锥虫病传播的创新战略奠定基础,例如制定有针对性的干预措施,以扰乱寄生虫在三蝽载体内的增殖和传播。
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来源期刊
Parasites & Vectors
Parasites & Vectors 医学-寄生虫学
CiteScore
6.30
自引率
9.40%
发文量
433
审稿时长
1.4 months
期刊介绍: Parasites & Vectors is an open access, peer-reviewed online journal dealing with the biology of parasites, parasitic diseases, intermediate hosts, vectors and vector-borne pathogens. Manuscripts published in this journal will be available to all worldwide, with no barriers to access, immediately following acceptance. However, authors retain the copyright of their material and may use it, or distribute it, as they wish. Manuscripts on all aspects of the basic and applied biology of parasites, intermediate hosts, vectors and vector-borne pathogens will be considered. In addition to the traditional and well-established areas of science in these fields, we also aim to provide a vehicle for publication of the rapidly developing resources and technology in parasite, intermediate host and vector genomics and their impacts on biological research. We are able to publish large datasets and extensive results, frequently associated with genomic and post-genomic technologies, which are not readily accommodated in traditional journals. Manuscripts addressing broader issues, for example economics, social sciences and global climate change in relation to parasites, vectors and disease control, are also welcomed.
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