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。含有粘蛋白的黏液层形成了保护毯，代表了胃肠道的前线防御。粘蛋白被认为在许多肠道感染（包括许多寄生虫感染）中对宿主保护起重要作用。获得杯状细胞生物学和粘蛋白产生的精确知识对于理解肠道对各种感染因子的防御机制至关重要。肠道菌群是生活在胃肠道内的微生物的集合，主要由细菌组成。Nod蛋白是先天免疫受体，通过检测细菌细胞壁的肽聚糖成分，在识别细菌感染中起重要作用。在这个应用中，我建议研究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。本课题将探索Nod蛋白在调节肠道杯状细胞生物学中发挥重要作用，肠道寄生虫感染通过改变肠道菌群组成和影响肠道菌群-Nod轴影响杯状细胞功能。本文将通过粘蛋白产生细胞系和寄生虫感染动物研究Nod蛋白在杯状细胞中的表达和功能，以及肠道菌群-Nod轴在肠感染杯状细胞生物学调节中的作用。本研究将为肠道杯状细胞生物学和粘蛋白产生机制的研究提供新的信息。除了在杯状细胞生物学中提供寄生虫-肠道菌群相互作用的见解外，本研究还将为加强我们对肠道寄生虫感染的肠道防御机制的理解提供重要信息

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.The proposed research will provide us novel information on intestinal goblet cell biology and on mechanism of mucin production. In addition to providing insight into parasite-gut flora interaction in goblet cell biology this research will give us important information in relation to enhancing our understanding of intestinal defense mechanisms in enteric parasitic infection