Symbiosis and Immunity in the Tsetse Fly

描述(申请人提供)：细菌共生在自然界中无处不在，但到目前为止，还没有进行过多少研究来确定这些关系背后的生理机制。昆虫代表了一组先进的多细胞有机体，它们拥有有据可查的共生联系。一种这样的昆虫，采采蝇(Glossina spp.)，含有两种由母体传播的细菌共生体，互惠共生的Wigglesworth和共生的Sodalis，它们与维持宿主的整体健康密切相关。具体地说，当未成熟的采采蝇在没有内源微生物区系的情况下发育时，随后的“非共生”成虫非常容易感染通常非致病性的大肠杆菌。这种易感表型的特点是细胞和体液免疫高度受损。在这项研究中，我们将采用下一代测序技术来研究共生菌诱导采采症免疫系统成熟的分子机制。这种苍蝇是致病非洲锥虫的唯一媒介，它会在人类中引起昏睡病，在家养动物中引起Nagana。通过完成这项工作所获得的知识可以用来减少通过采采赛以及其他寄生细菌和媒介人类病原体的昆虫(如蚊子)传播疾病。此外，与采采树共生菌诱导免疫的遗传学相关的基本概念对哺乳动物免疫学可能是至关重要的。 与公共健康相关：采采蝇体内含有共生细菌，可诱导宿主免疫系统的发育。我们将使用这个模型系统来更好地了解共生调节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，从人类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.