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

鼠艾滋病模型：C Parvum 益生菌，机会性感染： MAIDS：TCR 基因：

• 批准号: 6604785
• 负责人: JOHN I ALAK
• 金额: $ 11.63万
• 依托单位: TUSKEGEE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-06-01 至 2003-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6604785
• 关键词: AIDS; Mammalia; communicable diseases; immunology; inborn metabolism disorder; inflammation; lymphatic system; minority institution research support; model design /development; vaccines; virus

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.

本提案的总体目标是研究 宿主/病原体在粘膜表面相互作用并发展 最大化保护性粘膜免疫的预防策略 对小隐孢子虫 (C parvum) 的反应。 我们将开发和 维持小鼠获得性免疫缺陷综合征的小鼠模型 (MAIDS)，将用于研究帕尔姆念珠菌的发病机制；一个 通常与艾滋病相关的潜在病原体。 开发 MAIDS模型，C57BI_16雌性小鼠获得免疫抑制 接种LP-BM5；然后在 3 个月后用 C parvum 进行挑战 LP-BM5 感染。 实验诱导隐孢子虫病的研究 使用该模型，将作为评估各种 预防这种机会性疾病的疗法如我们之前的 研究证实，感染 LP-BM5 的小鼠会出现 持续存在大量卵囊的实验性隐孢子虫病 排泄在粪便中。 由于艾滋病在全球范围内频繁传播 与机会性感染有关，包括隐孢子虫病， 控制与艾滋病相关的机会性疾病对于 减轻人类痛苦，以尽量减少社会和 对社会的经济影响。 我们的长期目标是发展 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。 目前尚无有效治疗方法 隐孢子虫病已有报道。 我们将实现以下目标 这些研究的具体目标：阐明细胞的作用 通过确定角色，在该 MAIDS 模型中对微小念珠菌进行肠道免疫 肠道 (1) 上皮内 (EEL) 的表型频率和表型频率 (2) 固有层 (LPL) 亚群（CD4'、CD8、IgA、IgG' 和 IgM') 和细胞因子（TNF-a、IFN-y、IL-1、IL-2、4、5 和 10）的产生 C 后小挑战。 (3)评价乳酸菌的功效 罗伊氏菌和嗜酸乳杆菌作为益生菌用于控制 隐孢子虫病和 (4) 评估益生菌的功效和 (5) 同时施用小牛藤以控制 隐孢子虫病。 从这些研究中获得的结果将是 与控制新疗法的开发相关 免疫功能低下者的隐孢子虫病和其他机会性疾病 个人，尤其是艾滋病患者。