Host-pathogen interactions in targeting Wolbachia to the stem cell niche

描述(申请人提供)：虽然沃尔巴克氏菌感染在大多数节肢动物中发现，并在许多寄生虫病中具有临床重要性，但对其传播的细胞机制知之甚少。 我以前已经证明，无论是在新的接种中，还是在已建立的感染株系中，沃尔巴克氏菌都优先分布在苍蝇卵巢中含有体细胞干细胞的区域。对体细胞干细胞生态位的趋向性提供了一条以前未被发现的到达新宿主胚系的途径。干细胞生态位继续成为沃尔巴克氏菌聚集的场所，这表明沃尔巴克氏菌的水平和垂直传播可能具有共同的机制。在这里，我建议使用这个系统来研究宿主-病原体相互作用的分子和细胞机制。该提案的目的是阐明干细胞生态位趋向性所涉及的细菌和宿主因素。为了实现这一目标，我将使用可用于果蝇研究的分子、遗传和细胞生物学工具。我打算回答的问题是： 1.宿主细胞过程的操纵：生态位感染对干细胞活性的影响 2.细菌和宿主信号系统之间的相互作用：控制干细胞功能的信号通路的遗传破坏 3.生态位定位的进化保守性：鉴定不同寄主-寄生虫组合中干细胞的生态位趋向性。 4.干细胞生态位趋向性的确定：宿主和细菌因素的调查。 外行人摘要： 沃尔巴克氏菌感染昆虫和其他无脊椎动物。它们与河盲症和其他人类疾病有关。这种细菌通过母体在卵子中代代相传。我已经证明，沃尔巴克氏杆菌注射到未受感染的宿主中，目标是卵巢的干细胞壁龛区域，从那里它可以直接感染生殖系。同样的途径对于在长期感染中继续保持细菌可能很重要。对这种传播途径的进一步研究应该会产生关于这种细菌寄生虫的进化和生态的信息，以及用于病虫害控制的细胞生物学策略。

DESCRIPTION (provided by applicant): Although Wolbachia infections are found in most Arthropods and are of clinical importance in many parasitic diseases, very little is known about the cellular mechanisms responsible for their transmission. I have previously shown that Wolbachia preferentially populates the region of fly ovary containing the somatic stem cells, both in new inoculations and in established infected lines. Tropism for the somatic stem cell niche provides a previously undetected route to reach the germ line of new hosts. That the stem cell niche continues to be a site of accumulation suggests the possibility that horizontal and vertical transmission of Wolbachia may share common mechanisms. Here I propose to investigate the molecular and cellular mechanisms underlying host-pathogen interaction using this system. The goal of the proposal is to elucidate the bacterial and host factors involved in tropism for the stem cell niche. Towards this goal I will use molecular, genetic and cell biological tools available for Drosophila research. The questions that I intend to address are: 1. Manipulation of host cell processes: Effects of niche infection in stem cell activity 2. Interplay between bacteria and the host signaling system: Genetic disruption of signaling pathways controlling stem cell function 3. Evolutionary conservation of niche targeting: Identification of stem cell niche tropism in different host- parasite associations. 4. Determination of stem cell niche tropism: Investigation of host and bacterial factors. Layman summary: Wolbachia bacteria infect insects and other invertebrates. They are associated with river blindness and other human diseases. The bacteria are maternally transmitted in the egg from one generation to the next. I have shown that Wolbachia injected into uninfected host target the stem cell niche region of the ovary, from where it can directly infect the germ line. The same route may be important for continued maintenance of the bacteria in long-term infections. Further investigation of such transmission routes should yield information on evolution and ecology of this bacterial parasite, as well as cell biological strategies for pest and disease control.