Project 2

由原生动物寄生虫贾第鞭毛虫引起的人类贾第鞭毛虫病是最流行的肠道疾病之一， 寄生性原生动物感染在全球范围内，发达国家的患病率为2-5%， 30%在发展中国家。人类感染是通过摄入四核包囊沿着 与污染的食物或水和营养形式的寄生虫或滋养体定殖的近端 小肠部分，尤指十二指肠和空肠。人类感染的症状是 其特征在于胃肠道症状，可能包括腹部绞痛、肠胃气胀、腹泻、恶心， 在临床和亚临床病例中发生吸收不良综合征，并可能导致无法茁壮成长和/或 发育迟缓，尤其是儿童。大多数人类贾第虫病病例是自限性的， 在免疫功能正常的个体中暴露后数周内自发发生，表明 有效的抗贾第虫免疫足以清除G.人类的尿道感染。我们有 发现在主要肠道亚细胞中趋化因子/趋化因子受体信号通路的非冗余功能， 在整个肠道中，也是如此。与微环境差异相一致 在小肠和结肠之间，胆汁酸（BA）的差异表达，作为 胆固醇催化剂，代表了形成肠道内稳态的主要微环境线索之一 和炎症。使用人类贾第虫病的小鼠模型， 我们将研究BA在沿着肠道的区室化免疫应答中所起的作用。 道。这些研究的成功完成将提高我们对这些机制的理解， 免疫细胞被印记并归巢到肠道亚隔室，并将进一步提供对 在感染和非感染（即， IBD，乳糜泻）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.