Project 2

人类贾第鞭毛虫病是由原虫寄生虫十二指肠贾第鞭毛虫引起的，是最常见的肠道疾病之一。 全球寄生性原生动物感染，发达国家的流行率从2%到5%不等，20%- 30%在发展中国家。人类感染是由摄入四核包囊引起的。 受污染的食物或水，以及寄生虫或滋养体的繁殖体在近端定居 小肠的一部分，尤指十二指肠和空肠人类的症状感染是 以胃肠道症状为特征的，可能包括腹部痉挛、腹胀、腹泻、恶心、 在临床和亚临床病例中出现吸收不良综合征，并可能导致发育不良和/或 发育迟缓，尤指儿童发育迟缓大多数人类贾第鞭毛虫病病例都是自限性的，并已得到解决 在免疫能力强的人暴露后的几周内自发地，表明发生了 一种有效的抗贾第虫免疫，足以清除人类十二指肠球虫感染。我们有 趋化因子/趋化因子受体信号通路在主要肠道亚型中的非冗余功能 以及横跨整个肠道。与微环境差异相一致 在小肠和结肠之间，胆汁酸(BAS)的差异表达，作为 胆固醇分解代谢是影响肠道内环境平衡的主要微环境因素之一 以及这两个主要解剖亚室的炎症。使用人类贾第鞭毛虫病的小鼠模型， 我们将研究BA在肠道分区免疫反应中所起的作用 一条小路。成功完成这些研究将提高我们对以下机制的理解 免疫细胞被印记和归宿到肠道亚室，并将进一步提供对 在感染性和非感染性(即 IBD，乳糜泻)在人类的环境中。

Human giardiasis, caused by the protozoan parasite Giardia duodenalis, is one of the most prevalent enteric parasitic protozoan infections globally, with prevalence rates ranging from 2-5% in the developed world and 20- 30% in the developing countries. Human infections are initiated by the ingestion of quadrinucleate cysts along with contaminated food or water and the vegetative forms of the parasite or trophozoites colonize the proximal portions of the small intestine, especially the duodenum and jejunum. Symptomatic infections in humans are characterized by gastrointestinal symptoms that may include abdominal cramps, flatulence, diarrhea, nausea, with a malabsorption syndrome occurring in clinical and subclinical cases and may result in failure to thrive and/or stunted growth, especially in children. Most cases of human giardiasis are self-limiting and are resolved spontaneously within weeks following exposure in immunocompetent individuals, indicating the development of an effective anti-Giardia immunity sufficient for the clearance of G. duodenalis infections in humans. We have found non-redundant functions for chemokine/chemokine receptor signaling pathways in major intestinal sub- compartments as well as across the entire intestinal tract. Consistent with the microenvironmental differences between the small intestine and the colon, the differential expression of bile acids (BAs), as the end-products of cholesterol catabolism, represents one of the major microenvironmental cues shaping intestinal homeostasis and inflammation in these two main anatomical sub-compartments. Using a mouse model of human giardiasis, we will investigate the roles played by the BA in the compartmentalized immune responses along the intestinal tract. Successful completion of these studies will improve our understanding of the mechanisms by which immune cells are imprinted and homed to the intestinal sub-compartments and will further provide insights into the development of novel preventive and therapeutic targets in the context of infections and non-infectious (i.e. IBD, celiac disease) settings in humans.