Innate Immunity to Cryptosporidium parvum Infection

描述（由申请方提供）：隐孢子虫引起的腹泻 细小病毒（Cp）是世界范围内发病和死亡的主要原因， 没有有效的治疗方法。 免疫缺陷者尤其 Cp感染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（IFN γ）依赖性机制。 本提案的目标 是：a）鉴定快速产生的IFN γ的来源，和B）显示 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 也可用于在野生型C57 B1/6小鼠中定位IFN γ产生细胞。 在 具体目的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。 来自IFN γ/-和野生型小鼠的T细胞过继转移的作用 RAG -/-小鼠。 在具体目标3中，NK T细胞和CD 1在免疫调节中的作用。 对Cp感染的耐药性，将通过挑战CD 1d-/-和NK T来定义 细胞缺陷动物与Cp. 感染Cp的IEC的体外共培养和 IEL将用于显示CD 1d对于这种相互作用是必需的。 更好 了解小鼠对Cp感染的先天免疫可能导致新的 治疗这种疾病的方法，没有有效的 疗法

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.