Mammalian African trypanosome VSG coat enhances tsetse's vector competence
Mammalian African trypanosome VSG coat enhances tsetse's vector competence
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DOI：
10.1073/pnas.1600304113
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发表时间：
2016-06-21
影响因子：
11.1
通讯作者：
Aksoy, Serap
中科院分区：
文献类型：
--
作者：
Aksoy, Emre;Vigneron, Aurelien;Aksoy, Serap
采采蝇是非洲锥虫的生物媒介，非洲锥虫是导致撒哈拉以南非洲人和动物锥虫病的原生动物寄生虫。目前，由于寄生在哺乳动物体内的寄生虫外壳表面糖蛋白(VSG)的抗原变异，目前还没有可用的疫苗来预防疾病。因此，人们正在探索干扰采采树媒介中寄生虫的发展，以减少疾病传播。当寄生虫试图在采采族的中肠定居时，感染的一个主要瓶颈就会发生。影响这一瓶颈的一个关键因素是苍蝇的围食基质(PM)，这是一种排列在中肠内的半渗透的几丁质屏障。使锥虫能够越过这一障碍的机制目前尚不清楚。在这里，我们确定了当寄生虫进入采采人的肠道时，从锥虫体内释放的VSG分子被心脏细胞内化--负责产生PM的组织VSG内化导致tsetse microRNA(mir-275)表达减少，并干扰Wnt信号通路和易洛魁/IRX转录因子家族。这种干扰降低了PM屏障的功能，并在感染过程的早期促进了肠道寄生虫的定植。哺乳动物寄生虫外壳蛋白控制昆虫中肠的动态平衡是一种新的功能，表明VSG在锥虫生物学中具有双重作用--促进通过哺乳动物宿主和昆虫载体的传播。我们详细介绍了锥虫感染过程中的关键步骤，这些步骤可以作为减少采采虫媒介能力和疾病传播的新靶点。
Tsetse flies are biological vectors of African trypanosomes, the protozoan parasites responsible for causing human and animal trypanosomiases across sub-Saharan Africa. Currently, no vaccines are available for disease prevention due to antigenic variation of the Variant Surface Glycoproteins (VSG) that coat parasites while they reside within mammalian hosts. As a result, interference with parasite development in the tsetse vector is being explored to reduce disease transmission. A major bottleneck to infection occurs as parasites attempt to colonize tsetse's midgut. One critical factor influencing this bottleneck is the fly's peritrophic matrix (PM), a semipermeable, chitinous barrier that lines the midgut. The mechanisms that enable trypanosomes to cross this barrier are currently unknown. Here, we determined that as parasites enter the tsetse's gut, VSG molecules released from trypanosomes are internalized by cells of the cardia-the tissue responsible for producing the PM. VSG internalization results in decreased expression of a tsetse microRNA (mir-275) and interferes with the Wnt-signaling pathway and the Iroquois/IRX transcription factor family. This interference reduces the function of the PM barrier and promotes parasite colonization of the gut early in the infection process. Manipulation of the insect midgut homeostasis by the mammalian parasite coat proteins is a novel function and indicates that VSG serves a dual role in trypanosome biology-that of facilitating transmission through its mammalian host and insect vector. We detail critical steps in the course of trypanosome infection establishment that can serve as novel targets to reduce the tsetse's vector competence and disease transmission.