CRYPTOSPORIDIUM INTERACTION WITH MAMMALIAN CELLS

隐孢子虫是一种新发现的人类病原体， 在免疫功能低下的患者中出现严重的持续性肠炎， 特别是患有后天免疫缺陷综合症（艾滋病）的人， 在免疫正常的人中， 主持人 随着越来越多的医生寻找病原体， 在免疫功能低下和正常人群中均报告了隐孢子虫病病例 个人继续上升。 目前还没有已知的有效的 治疗疾病。 人类宿主防御的因素是成功的关键 隐孢子虫的根除还没有被描述。 很少有线索 通过研究临床和组织病理学特征， 人类疾病，主要是免疫功能低下（AIDS）患者和动物。 目前可用的数据表明：a）T和B细胞介导的 免疫力在宿主防御该病原体中发挥作用，以及B） 免疫的细胞和体液成分与免疫系统密切相关。 靶细胞：肠上皮细胞，以成功防御 这个寄生虫。 隐孢子虫致病机制的实验研究 免疫发病机制受到以下因素的严重阻碍：a）缺乏体外 培养该生物体的方法，B）小尺寸和复杂的生命 寄生虫的周期，以及c）缺乏有症状的小动物模型 疾病。 在过去的两年里，我们成功地开发了一个 隐孢子虫-细胞相互作用的体外研究模型， 来自受感染患者粪便标本的卵囊。 我们还 成功地将该模型应用于隐孢子虫的体外培养。 这个项目的目的是进一步完善我们的模型，并使用它来 研究各种免疫和非免疫因素对 隐孢子虫与其宿主靶细胞-肠上皮细胞的相互作用。 因此，我们希望确定宿主防御的关键细胞和体液因素 其功能是根除完整宿主中的这种寄生虫， 在免疫受损的个体中不存在。 这些研究应进一步 我们对隐孢子虫病免疫发病机制的理解， 形成新的方法来成功地管理这一基础 疾病在未来

Cryptosporidium is a newly recognized human pathogen which is associated with severe, persistent enteritis in immunocompromised patients, particularly those with the acquired immunodeficiency syndrome (AIDS) and significant though self-limited illness in the immunologically normal host. As more physicians have looked for the pathogen, the number of reported cases of cryptosporidiosis in both immunocompromised and normal individuals has continued to rise. There is currently no known effective therapy for the disease. The factors of human host defense which are essential for successful eradication of Cryptosporidium have not been delineated. Few clues have been provided by study of the clinical and histopathologic features of the disease in man, primarily immunocompromised (AIDS) patients, and animals. Currently available data suggests that: a) both T and B-cell mediated immunity are functional in host defense against this pathogen, and b) cellular and humoral components of immunity act in close concert with the target cell: intestinal epithelium, to effect successful defense against this parasite. Laboratory investigation of cryptosporidial mechanisms of immunopathogenesis has been severely impeded by: a) lack of in vitro methods for cultivating the organism, b) the small size and complex life cycle of the parasite, and c) absence of a symptomatic small animal model of the disease. Over the past two years we have succeeded in developing a model for the study of Cryptosporidium-cellular interactions in vitro using oocysts derived from stool specimens of infected patients. We have also successfully adapted the model for cultivating Cryptosporidium in vitro. The intent of this project is to further refine our model and use it to investigate the effects of various immune and non-immune factors on the interaction of Cryptosporidium with its host target cell - the enterocyte. We hope thus to define key cellular and humoral factors of host defense which function to eradicate this parasite in the intact host and which are absent in the immunocompromised individual. These studies should further our understanding of the immunopathogenesis of cryptosporidiosis and also form the basis for novel approaches to successful management of this disease in the future.