INTERACTIONS OF E HISTOLYTICA WITH HOST MUCOSAL DEFENSES

溶组织内阿米巴是寄生虫感染致死的第三大原因。 疾病，但决定菌株致病能力的因素 对侵袭性阿米巴病了解很少。研究主要集中在 与肠粘膜相互作用的差异 潜在入侵性E. histolytica和肠道原虫E. dispar，应该提供重要的见解，基本主机防御中， 肠子为了成功入侵。E.溶组织滋养体必须 绕过许多免疫和非免疫宿主对sIgA的防御 以及活化的中性粒细胞及其氧化的杀微生物活性， 产品.我们将评估E. histolytica和E. dispar与宿主粘膜防御通过： 目标1.评价sIgA在预防阿米巴感染中的作用 评估免疫sIgA对滋养体结合和对 诱导炎性细胞因子应答，由E. 溶组织半胱氨酸蛋白酶，以及特异性sIgA对 在人肠异种移植物中的侵袭。 目标二。比较E. histolytica和E.不适用于 通过测试中性粒细胞及其氧化能力的氧化攻击 产品杀死E. histolytica和E. dispar，比较抗氧化剂 活性E. histolytica、溶组织E. dispar和G. Lamblia，确定 sIgA或IgG阻断抗氧化活性的能力，并评估 抗氧化基因的调控。 目标3.评价阻断抗氧化活性对阿米巴的影响 通过消除29 kD抗氧化剂和超氧化物的表达来侵袭 歧化酶E. histolytica的反义RNA介导，抑制E.与...争论 E.组织溶解，并测试的重要性， 抗氧化活性对人肠异种移植物侵袭的影响。 通过对寄生虫和宿主因素提供重要的新见解， 确定E. histolytica和E. 尽管如此，这些研究将增加我们对基本宿主的认识， 肠道防御系统

Entamoeba histolytica is the third leading cause of death from parasitic disease, yet the factors which determine the ability of a strain to cause invasive amebiasis are poorly understood. Studies focused on the differences between the interactions with the intestinal mucosal of potentially invasive E. histolytica and the commensal protozoan, E. dispar, should provide important insights into basic host defenses in the bowel. For successful invasion. E. histolytica trophozoites must circumvent a number of immune and non-immune host defenses against sIgA and the microbicidal activity of activated neutrophils and their oxidative products. We will evaluate the interactions of E. histolytica and E. dispar with host mucosal defenses by: Aim 1. Evaluate the role of sIgA in protection against amebic infection by evaluating the effect of immune sIgA on trophozoite binding and on the induction of an inflammatory cytokine response, cleavage of sIgA by the E. histolytica cysteine proteinase, and the effect of specific sIgA on invasion in human intestinal xenografts. Aim 2. Compare the susceptibility of E. histolytica and E. dispar to oxidative attack by testing the ability of neutrophils and their oxidative products to kill E. histolytica and E. dispar, comparing the antioxidant activity of E. histolytica, E. dispar and G. lamblia, determining the ability of sIgA or IgG to block antioxidant activity, and evaluating the regulation of the antioxidant gene. Aim 3. Evaluate the effect of blocking antioxidant activity on amebic invasion by ablating expression of the 29 kD antioxidant and superoxide dismutase in E. histolytica by antisense RNAs, transfecting E. dispar with the antioxidant gene for E. histolytica, and testing the importance of antioxidant activity on invasion of human intestinal xenografts. By providing important new insights into parasite and host factors which determine the outcome of infection invade with E. histolytica and E. dispar, these studies will increase our knowledge of the basic host defenses in the bowel.