Symbiosis and Immunity in the Tsetse Fly

描述（由申请人提供）：细菌共生在自然界中无处不在，但迄今为止，很少有研究确定这些关系背后的生理机制。昆虫代表了一群先进的多细胞生物，它们有着充分记录的共生关系。其中一种昆虫，采采蝇（舌蝇属），携带着两种通过母体传播的共生细菌，即互惠的威格氏菌和共生的索达氏菌，它们与维持宿主的整体健康密切相关。具体来说，当未成熟采采蝇在缺乏内源性微生物群的情况下发育时，随后的“非共生”成虫对通常非致病性大肠杆菌的感染高度敏感。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，我们将利用新一代测序技术来研究采采蝇共生诱导免疫系统成熟的分子机制。该蝇是非洲锥虫致病性的唯一媒介，可在人类和家畜中引起昏睡病。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，这些昆虫是共生细菌和人类病原体的载体。此外，与采采中共生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重要意义。

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.