Symbiosis and Immunity in the Tsetse Fly

描述（由申请人提供）：细菌共生体在自然界中普遍存在，但迄今为止，很少有研究已经进行，以确定这些关系的生理机制。昆虫代表了一组先进的多细胞生物体，它们具有有据可查的共生关系。一种这样的昆虫，采采蝇（舌蝇属），窝藏2母体传播的细菌共生体，互惠Wigglesophagia和Sodalis，密切参与维持其主机的整体健身。具体来说，当未成熟的采采蝇在缺乏其内源性微生物群的情况下发育时，随后的“非共生”成虫对正常非致病性E.杆菌这种易感表型的特征在于高度受损的细胞和体液免疫。在这项研究中，我们将采用新一代测序技术来研究采采蝇共生体诱导免疫系统成熟的分子机制。这种苍蝇是唯一的致病性非洲锥虫的媒介，它会引起人类的昏睡病和驯养动物的Nagana。通过完成这项工作获得的知识可用于减少通过采采蝇以及其他昆虫（如蚊子）传播的疾病，这些昆虫体内有共生细菌并携带人类病原体。此外，与采采蝇共生体诱导免疫的遗传学相关的基本概念可能对哺乳动物免疫学具有根本的重要性。 公共卫生相关性：采采蝇体内有共生细菌，可以诱导宿主免疫系统的发育。我们将使用这个模型系统，以获得一个更好的理解的基础共生体介导的动物免疫发展的分子机制。这些信息将适用于控制广泛的人类病理学，从非洲锥虫病到克罗恩病。

DESCRIPTION (provided by applicant): Bacterial symbioses are ubiquitous in nature, yet to date few studies have been performed to determine the physiological mechanisms that underlie these relationships. Insects represent a group of advanced multi-cellular organisms that harbor well- documented symbiotic associations. One such insect, the tsetse fly (Glossina spp.), harbors 2 maternally-transmitted bacterial symbionts, mutualistic Wigglesworthia and commensal Sodalis, that are intimately involved in maintaining the overall fitness of their host. Specifically, when immature tsetse flies develop in the absence of their endogenous microbiota, subsequent 'aposymbiotic' adults are highly susceptible to infection with normally non-pathogenic E. coli. This susceptible phenotype is characterized by highly compromised cellular and humoral immunity. In this study we will next generation sequencing technologies to investigate the molecular mechanisms that underlie symbiont-induced immune system maturation in tsetse. This fly serves as the sole vector pathogenic African trypanosomes, which cause sleeping sickness in humans and Nagana in domesticated animals. Knowledge gained by completing this work can be used to reduce disease transmission through tsetse, as well as other insects (such as mosquitoes) that house symbiotic bacteria and vector human pathogens. Furthermore, basic concepts related to the genetics that underlie symbiont-induced immunity in tsetse may be of fundamental importance to mammalian immunology. PUBLIC HEALTH RELEVANCE: Tsetse flies harbor symbiotic bacteria that induce the development of their host's immune system. We will use this model system to acquire a better understanding of the molecular mechanisms that underlie symbiont-mediate development of animal immunity. This information will be applicable to controlling a wide range of human pathologies, ranging from Human African trypanosomiasis to Crohn's disease.