Role of Nod Proteins in Regulation of Intestinal Goblet Cell Biology in Enteric Parasitic Infection

杯状细胞存在于整个胃肠道，是肠道粘蛋白的主要来源。含有粘蛋白的粘液层形成了一层保护毯，代表着胃肠道的前线防御。粘蛋白被认为在许多肠道感染中发挥着重要的宿主保护作用，包括许多寄生虫感染。掌握有关杯状细胞生物学和粘蛋白产生的精确知识，对于了解肠道对各种感染性病原体的防御机制至关重要。肠道菌群是生活在我们的胃肠道内的微生物的集合，主要由细菌组成。NOD蛋白是一种先天免疫受体，通过检测细菌细胞壁的一种称为肽聚糖的成分，在识别细菌感染方面发挥重要作用。在这个应用中，我建议检查一个将寄生虫感染与肠道菌群和先天免疫受体联系起来的模型，以扩展我们对肠道杯状细胞生物学和粘蛋白产生的理解。这项资助将探索NOD蛋白在肠道杯状细胞生物学调节中的重要作用，肠道寄生虫感染通过改变肠道菌群组成和影响肠道菌群-结节轴来影响杯状细胞的功能。利用粘蛋白产生细胞系和寄生虫感染动物，研究肠道感染时杯状细胞中NOD蛋白的表达和功能，以及肠道菌群-节点轴在调节杯状细胞生物学中的作用。

Goblet cells are present throughout the gastrointestinal (GI) tract and are the main source of mucins in the gut. Mucus layer containing mucins forms a protective blanket and represents the front line of defense in the GI tract. Mucins are considered to play an important role in host protection in a number of enteric infections, including many parasitic infections. Gaining precise knowledge on goblet cell biology and mucin production is critical in understanding intestinal defense mechanism against various infectious agents. Gut flora are the collection of microorganisms that live within our GI tract and are predominantly made up of bacteria. Nod proteins are innate immune receptors and important role in recognition of bacterial infection through their detection of a component of the bacterial cell wall called peptidoglycan. In this application I propose to examine a model that links parasitic infection to gut flora and innate immune receptors to extend our understanding of intestinal goblet cell biology and mucin production. This grant will explore the idea that Nod proteins play an important role in the regulation of intestinal goblet cell biology, and enteric parasite infection influences goblet cell function by changing the composition of gut flora and influencing gut flora-Nod axis. Expression and function of Nod proteins in goblet cells and the role of gut flora-Nod axis in regulation of goblet cell biology in an enteric infection will be investigated by utilizing mucin producing cell line and parasite infected animals.