Innate Immunity to Cryptosporidium parvum Infection

对小隐孢子虫感染的先天免疫

• 批准号: 6465481
• 负责人: BRETT A LEAV
• 金额: $ 11.37万
• 依托单位: TUFTS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6465481
• 关键词: CD1 molecule; Cryptosporidium; cell transplantation; cellular immunity; chemical structure function; cryptosporidiosis; disease /disorder model; enzyme linked immunosorbent assay; flow cytometry; gene expression; genetically modified animals; host organism interaction; immunocytochemistry; immunogenetics; immunoregulation; interferon gamma; laboratory mouse; lymphocyte; microorganism immunology; nonhuman therapy evaluation; parasite infection mechanism; passive immunization; protein structure function; protozoal genetics; statistics /biometry; western blottings

DESCRIPTION (provided by applicant): Diarrhea caused by Cryptosporidium parvum (Cp) is a major cause of morbidity and mortality worldwide for which there is no effective treatment. Immunodeficient persons are at particular risk of the more severe complications of Cp infection, including cholangitis and malnutrition. Scid mice are initially resistant to Cp infection through an interferon gamma (IFNy)-dependent mechanism. The goals of this proposal are to: a) identify the source of rapidly produced IFNy, and b) to show that these cells are necessary for the resistance of mice to acute Cp infection. The relative importance of CD 1 and NK T cells in resistance to Cp challenge will be determined. In specific aim 1, immunohistochemistry and FACS will also be used to localize IFNy-producing cells in wild-type C57Bl/6 mice. In specific aim 2, RAG -/- mice will be used to determine to role of T cells in this acute resistance to Cp infection. This will be confirmed by comparing the effect of the adoptive transfer of T cells from IFNy /- and wild-type mice into RAG -/- mice. In specific aim 3, the roles of NK T cells and CDl in resistance to Cp infection, will be defined by challenging CD1d -/- and NK T cell deficient animals with Cp. In-vitro co-culture of Cp-infected IECs and IELs will be used to show that CD1d is necessary for this interaction. Better understanding of innate immunity to Cp infection in mice may lead to novel therapeutic approaches to this disease for which there is no effective therapy.

描述（由申请人提供）：隐孢子虫引起的腹泻 parvum (Cp) 是全世界发病和死亡的主要原因 没有有效的治疗方法。 免疫力低下的人尤其 发生更严重的 Cp 感染并发症（包括胆管炎）的风险 和营养不良。 Scid 小鼠最初通过以下方式抵抗 Cp 感染： 干扰素γ (IFNy) 依赖性机制。 本提案的目标 目的是：a) 确定快速产生的 IFNy 的来源，以及 b) 证明 这些细胞对于小鼠抵抗急性 Cp 感染是必需的。 CD 1 和 NK T 细胞在抵抗 Cp 攻击中的相对重要性 将被确定。 在具体目标 1 中，免疫组织化学和 FACS 将 也可用于定位野生型 C57Bl/6 小鼠中产生 IFNγ 的细胞。 在 具体目标 2，RAG -/- 小鼠将用于确定 T 细胞在 这种对Cp感染的急性抵抗力。 这将通过比较来证实 IFNγ/- 和野生型小鼠 T 细胞过继转移的效果 进入 RAG -/- 小鼠。 在具体目标 3 中，NK T 细胞和 CD1 在 对 Cp 感染的抵抗力，将通过挑战 CD1d -/- 和 NK T 来定义 具有 Cp 的细胞缺陷动物。 Cp 感染的 IEC 的体外共培养和 IEL 将用于表明 CD1d 对于这种相互作用是必要的。 更好的 了解小鼠对 Cp 感染的先天免疫可能会带来新的发现 这种疾病目前还没有有效的治疗方法 治疗。