Innate Immunity to Cryptosporidium parvum Infection

对小隐孢子虫感染的先天免疫

• 批准号: 6623418
• 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/6623418
• 关键词: CD1 molecule; Cryptosporidium; cell transplantation; cellular immunity; 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