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

本建议的总体目标是研究 粘膜表面的宿主/病原体相互作用， 最大化保护性粘膜免疫的预防策略 隐孢子虫（Cryptosporidiumparvum） 创新和 维持鼠获得性免疫缺陷综合征的鼠模型 （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。 发展 MAIDS模型中，C57BI_16雌性小鼠被免疫抑制。 用LP-BM 5接种;然后在接种后3个月用小隐孢子虫攻毒 LP-BM 5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， 研究已经证实，感染LP-BM 5的小鼠， 持续性实验性隐孢子虫病伴大量卵囊 在粪便中脱落。 由于艾滋病的传播是全球性的， 与包括隐孢子虫病在内的机会性感染有关， 控制与艾滋病有关的艾滋病至关重要， 减轻人类痛苦，以尽量减少社会和 对社会的经济影响。 我们的长远目标是发展 用于控制隐孢子虫的有效预防方案。 感染，特别是通过营养，免疫或 化疗干预。 到目前为止，还没有有效的治疗方法， 隐孢子虫病已被报道。 我们将实现以下目标 这些研究的具体目标：阐明细胞的作用， 通过确定在MAIDS模型中的作用， 肠上皮内（1）（EEL） 和（2）固有层（LPL）亚群（CD 4 ′、CD 8、伊加、IgG ′和 IgM '）和细胞因子（TNF-α、IFN-γ、IL-1、IL-2、4、5和10）的产生 小隐孢子虫感染后。 (3)评价乳酸菌的功效 reuteri和L.嗜酸乳杆菌作为益生菌用于控制 隐孢子虫病和（4）评价益生菌的功效和（5） 同时施用疫苗以控制 隐孢子虫病 这些研究的结果将 在开发新的治疗方法，以控制 隐孢子虫病和其他机会性疾病 尤其是艾滋病患者。

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.