Innate Immunity to Cryptosporidium parvum Infection

描述(申请人提供)：由隐孢子虫引起的腹泻 细小肺炎(Parvum，CP)是世界范围内发病率和死亡率的主要原因。 目前还没有有效的治疗方法。免疫缺陷者尤其是 CP感染的更严重并发症的风险，包括胆管炎 和营养不良。SCID小鼠最初通过以下途径抵抗CP感染 干扰素γ(IFNy)依赖的机制。这项提案的目标是 是：a)确定快速生产的IFNy的来源，以及b)表明 这些细胞是小鼠抵抗急性CP感染所必需的。 CD-1和NK-T细胞在抵抗CP攻击中的相对重要性 将会被确定。在特定的目标1中，免疫组织化学和流式细胞仪将 也可用于野生型C57BL/6小鼠体内产生干扰素的细胞的定位。在……里面 特异靶2，RAG-/-小鼠将被用来确定T细胞在 这种对CP感染的急性抵抗力。这将通过比较来确认 过继转移IFNY/-和野生型小鼠T细胞的作用 变成破烂不堪的老鼠。在特定目标3中，NK T细胞和CDL在 对CP感染的抵抗力将通过挑战CD1d-/-和NK T来定义 患有CP的细胞缺陷动物。铜绿假单胞菌感染的IECs和ECs的体外共培养 将使用IEL来证明CD1d对于这种相互作用是必要的。更好 了解小鼠对CP感染的先天免疫可能导致新的 对这种疾病没有有效治疗方法的治疗方法 心理治疗。

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.