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

描述（由申请人提供）：尽管沃尔巴克氏体感染在大多数节肢动物中发现，并且在许多寄生虫病中具有临床重要性，但对负责其传播的细胞机制知之甚少。 我以前已经表明，沃尔巴克氏体优先人口的区域苍蝇卵巢含有体干细胞，无论是在新的接种和建立感染线。体干细胞小生境的趋向性提供了一条以前未被发现的到达新宿主生殖系的途径。干细胞龛继续成为积累的场所，这表明沃尔巴克氏体的水平和垂直传播可能具有共同的机制。在这里，我建议调查的分子和细胞机制，宿主-病原体相互作用使用这个系统。该提案的目标是阐明干细胞生态位向性中涉及的细菌和宿主因素。为了实现这一目标，我将使用果蝇研究可用的分子，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：小生境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.生态位靶向的进化保守性：不同宿主-寄生虫关系中干细胞生态位向性的鉴定. 4.干细胞生态位向性的测定：宿主和细菌因素的研究。 Layman总结： 沃尔巴克氏体细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。这种细菌在卵中通过母体从一代传给下一代。我已经证明，注射到未感染宿主体内的沃尔巴克氏体靶向卵巢的干细胞龛区，从那里它可以直接感染生殖系。相同的途径可能对细菌在长期感染中的持续维持很重要。对这种传播途径的进一步调查应产生关于这种细菌寄生虫的进化和生态学的信息，以及用于害虫和疾病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.