MURINE AIDS MODEL: C PARVUM PROBIOTICS, OPPORTUNISTIC INFEC: MAIDS: TCR GENE:

这项建议的总体目标是研究 宿主/病原体在粘膜表面的相互作用及其发展 最大限度地提高保护性粘膜免疫的预防策略 微小隐孢子菌(C Parvum)的应答我们将发展和 建立小鼠获得性免疫缺陷综合征模型 (MAIDS)，将用于研究C parmm的发病机制；a 通常与艾滋病有关的潜在病原体。要开发 C57BI_16雌性小鼠免疫抑制 接种Lp-BM5；3个月后接种C-parvum Lp-BM5感染。实验性隐孢子虫病的研究 使用该模型，将作为评估各种 预防这种机会性疾病的治疗方法 研究证实，感染LP-BM5的小鼠会患上 持续实验性隐孢子虫病并有大量卵囊 从粪便中排出。由于艾滋病的传播是全球性的，而且频繁 与包括隐孢子虫病在内的机会性感染有关， 控制与艾滋病相关的机会性疾病至关重要 减轻人类痛苦，以最大限度地减少社会和 对社会的经济影响。我们的长远目标将是发展 控制隐孢子虫的有效预防方案。 感染，特别是通过营养、免疫治疗或 化疗干预。到目前为止，还没有有效的治疗方法 隐孢子虫病已有报道。我们将实现以下目标 这些研究中的特定目标：阐明细胞的作用 通过确定角色在该MAIDES模型中对微小C菌的肠道免疫 肠道(1)上皮内(鳗鱼)的表型频率 和(2)固有层(LPL)亚群(CD4‘、CD8、IgA、Ig G’和 IGM‘)和细胞因子(肿瘤坏死因子-α、干扰素-γ、白介素1、白介素2、4、5和10)的产生 C后抽签挑战赛。(3)乳酸菌的药效评价 鲁氏乳杆菌和嗜酸乳杆菌作为益生菌防治玉米赤眼病 隐孢子虫病和(4)评估益生菌的疗效和(5) 同时给药用于防治黄斑狼疮 隐孢子虫病。从这些研究中获得的结果将是 与控制肺炎的新疗法的开发有关 免疫受损的隐孢子虫病和其他机会性疾病 个人，特别是艾滋病患者。

The overall objective of this proposal is to study the host/pathogen interaction at mucosal surfaces and to develop prevention strategies that maximize protective mucosal immune responses to Cryptosporidiumum parvum (C parvum). We will develop and maintain a murine model for murine acquired immunodeficiency syndrome (MAIDS) which will be used to study the pathogenesis of C parmm; a potential pathogen commonly associated with AIDS. To develop the MAIDS model, C57BI_16 female mice win be immunosuppressed by inoculation with LP-BM5; then challenged with C parvum 3 months post LP-BM5 infection. Studies of experimentally induced cryptosporidiosis using this model, will serve as a relevant tool for evaluating various therapies for prevention of this opportunistic disease as our previous studies have confirmed that mice infected with LP-BM5, develop persistent experimental cryptosporidiosis with high numbers of oocysts shed in the feces. Since the spread of AIDS is global and frequently assoc iated with opportunistic infections including cryptosporidiosis, it is critical to control AIDS-related o0portunistic diseases to alleviate human suffering in order to minimize both social and economic impact on society. Our long range goal will be to develop effective prophylactic regimens for the control of Cryptosporidium. infection, especially through nutritional, immunotherapeutic or chemotherapeutic interventions. As yet, no effective treatment for cryptosporidiosis has been reported. We will achieve the following specific aims during these studies: elucidate the role of cellular gut immunity to C parvum in this MAIDS model by determining the roles and phenotypic frequencies of intestinal (1) intraepithelial (EEL's) and (2) lamina propria (LPL) subpopulations (CD4', CD8, IgA, IgG' and IgM') and cytokine (TNF-a , IFN-y, IL-1, IL-2, 4, 5 and 10) production post C parvum challenge. (3) evaluate the efficacy of Lactobacillus reuteri and L. acidophilus as probiotics for the control of cryptosporidiosis and (4) evaluate the efficacy of probiotics and (5) vavvines administered simultaneously for the control of cryptosporidiosis. Results obtained from these studies will be relevant in the development of new therapies for the control of cryptosporidiosis and other opportunistic diseases in immuncompromised individuals especially AIDS subjects.