HELICOBACTER PYLORI AND THE GASTRIC MICROBIAL COMMUNITY IN RHESUS MACAQUES

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 目标： 幽门螺杆菌是一种通常感染胃的细菌，它会在所有人中引起炎症(胃炎)，在一些人中会导致消化性溃疡疾病或胃癌。细胞毒素相关基因致病岛(CAG PAI)是目前研究最多的与胃癌和消化性溃疡相关的细菌因子。虽然幽门螺杆菌CAG PAI的细胞生物学在体外已经得到了广泛的研究，但它在体内的作用却鲜为人知。我们最近使用恒河猴模型证明了幽门螺杆菌以CAG PAI依赖的方式诱导抗菌宿主反应，其中包括上调胃粘膜中一系列天然免疫效应分子的表达。虽然幽门螺杆菌携带一种刺激抗细菌宿主防御的基因元素似乎有些自相矛盾，但它可能比其他胃部居民对这些效应物更具抵抗力，因此在炎症的胃中享有竞争优势。相反，已建立的微生物群落与宿主之间的相互作用可能调节幽门螺杆菌的成功定植。我们的具体目标是：(A)确定恒河猴胃微生物群落的特征，并比较野生型幽门螺杆菌及其同源CAG PAI敲除感染的影响，以及(B)确定减少胃微生物群落对幽门螺杆菌感染的影响。这些研究将有助于我们了解宿主和驻留微生物区系之间的相互作用，以及微生物群落成员之间的拮抗关系，这可能会加剧或缓解病原体对宿主的影响。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Objective: Helicobacter pylori is a bacterium that commonly infects the stomach, where it causes inflammation (gastritis) in all individuals and peptic ulcer disease or gastric cancer in some. The most intensively studied bacterial factor associated with the development of gastric cancer and peptic ulcer is the cytotoxin-associated gene pathogenicity island (cag PAI). While the cell biology of the H. pylori cag PAI has been studied extensively in vitro, its effects in vivo are poorly understood. We recently used the rhesus macaque model to demonstrate that H. pylori induces an antimicrobial host response in a cag PAI-dependent manner, which includes up-regulation of a suite of innate immune effectors molecules in the gastric mucosa. While it seems paradoxical that H. pylori would carry a genetic element that stimulates anti-bacterial host defenses, it is possible that H. pylori is more resistant to these effectors than other gastric inhabitants, and thus enjoys a competitive advantage in the inflamed stomach. Conversely, interactions between an established microbial community and the host may modulate successful colonization by H. pylori. Our specific goals are to: (a) characterize the microbial community of the stomach in the rhesus macaque and compare the effects of infection with wild-type H. pylori or its isogenic cag PAI knockout, and (b) determine the effects of reducing the gastric microbial community on infection with H. pylori. These studies will contribute to our understanding of the interplay between the host and resident microbiota, as well as antagonistic relationships between members of microbial communities, which may intensify or mitigate the impact of a pathogen on the host.