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

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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