The role of dendritic cells in T cell immunity to Cryptosporidium

树突状细胞在隐孢子虫 T 细胞免疫中的作用

• 批准号: 7806873
• 负责人: Hanping Feng
• 金额: $ 0.11万
• 依托单位: TUFTS UNIVERSITY BOSTON
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7806873
• 关键词: Antigens; Cell Communication; Cells; Cryptosporidiosis; Cryptosporidium; Cryptosporidium parvum; Dendrites; Dendritic Cells; Development; Enteral; Event; Exposure to; Foundations; Future; Goals; Human; Immune; Immune response; Immunity; In Vitro; Infection; Infection Control; Interferon Type II; Interleukin-12; Intervention; Intestines; Label; Lamina Propria; Lead; Link; M cell; Mediating; Mentored Research Scientist Development Award; Methods; Mus; Nature; Parasites; Play; Prevention; Prevention approach; Production; Resistance; Role; Sampling; Staining method; Stains; Structure of aggregated lymphoid follicle of small intestine; Surface; T-Cell Activation; T-Cell Proliferation; T-Lymphocyte; Up-Regulation; Vaccine Adjuvant; Vaccine Design; base; combat; cytokine; design; effective therapy; human morbidity; in vivo; migration; mortality; pathogen; response; trafficking; uptake

DESCRIPTION (provided by applicant): Title: The role of dendritic cells in T cell immunity to Cryptosporidium This application is for a Mentored Research Scientist Development Award (KO1) on Cryptosporidium, an enteric infection linked with serious human morbidity and mortality worldwide, and against which there is no effective therapy of prevention. Our goal is to elucidate the mechanisms by which immune cells initiate resistance against cryptosporidiosis with a view that a better understanding of the various components of the immune response will lead to development of effective vaccines and adjuvants to combat the infection in humans. Our central hypothesis is that DCs acquire parasite antigens when exposed to Cryptosporidium infection thereby priming specific T cell immunity. We base this on the observations that: 1) intestinal DCs located in the lamina propria directly sample pathogens by protruding dendrites into the gut lumen. DCs in Peyer's patch acquire intestinal antigens transferred by M cells; 2) IL-12, which is produced predominantly by dendritic cells, is critical in inducing gamma interferon and controlling C. parvum infection; 3) T cells, which can only be primed by dendritic cells, are indispensable in controlling the infection of Cryptosporidium. Based on these observations, the specific aims are designed to provide a comprehensive assessment of the nature of dendritic cell interaction with Cryptosporidium and induction of T cell immunity. They include: 1) Investigate Cryptosporidium antigen uptake by DCs following infection; 2) Determine the mode of activation and migration of DCs after exposure to Cryptosporidium infection; 3) Investigate dendritic cell-mediated T cell activation in response to Cryptosporidium infection. The proposed studies will provide the basis for understanding the mechanisms for the induction of T cell- mediated anti-Cryptosporidium immunity necessary for future design of vaccines and other methods of interventions.

描述（由申请人提供）： 职务名称：树突状细胞在T细胞免疫中对隐孢子虫的作用本申请是为了获得隐孢子虫的指导研究科学家发展奖（KO 1），隐孢子虫是一种肠道感染，与全球严重的人类发病率和死亡率有关，并且没有有效的预防治疗。我们的目标是阐明免疫细胞启动抵抗隐孢子虫病的机制，以期更好地了解免疫反应的各个组成部分，从而开发有效的疫苗和佐剂来对抗人类感染。我们的中心假设是，当暴露于隐孢子虫感染时，DC获得寄生虫抗原，从而引发特异性T细胞免疫。我们基于以下观察：1）位于固有层中的肠DC通过将树突突出到肠腔中来直接采样病原体。派伊尔结中的DC获得由M细胞转移的肠抗原; 2）IL-12主要由树突状细胞产生，在诱导γ干扰素和控制C. 3）T细胞在控制隐孢子虫感染中是不可缺少的，它只能被树突状细胞激活。基于这些观察，具体的目的是提供一个全面的评估树突状细胞与隐孢子虫相互作用的性质和诱导T细胞免疫。它们包括：1）研究感染后DC对隐孢子虫抗原的摄取; 2）确定暴露于隐孢子虫感染后DC的活化和迁移模式; 3）研究树突状细胞介导的T细胞活化对隐孢子虫感染的应答。拟议的研究将为理解T细胞介导的抗隐孢子虫免疫的诱导机制提供基础，这对于未来设计疫苗和其他干预方法是必要的。