The role of CD40L in resistance to enteric infection

CD40L在抵抗肠道感染中的作用

基本信息

批准号：
10470882
负责人：
CHRISTOPHER A HUNTER
金额：
$ 55.27万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-17 至 2026-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10470882
关键词：
Address Affect Agonist Antigens B-Lymphocytes CD4 Positive T Lymphocytes CD8-Positive T-Lymphocytes Cell physiology Cell surface Cells Cellular Immunology Child Chronic Communities Cryptosporidium Defect Dendritic Cells Development Disease Elements Engineering Enterobacteria phage P1 Cre recombinase Enterocytes Epithelial Epithelial Cells Etiology Event Experimental Models Gene Expression Profiling Gene Transfer Techniques Growth Human IFNGR1 gene Immune Immune response Immune system Immunity Immunocompromised Host Immunoglobulin Class Switching Infection Infection Control Inflammatory Inflammatory Response Interferon Type II Intestinal Diseases Lead Licensing Life Ligation Malignant - descriptor Mediating Modeling Mucosal Immunity Mucous Membrane Mus Mutation Outcome Parasite Control Parasites Parasitic infection Pathway interactions Patients Population Production Regulation Resistance Resistance to infection Role Signal Transduction Site Specificity Sterility Surveys T cell response T-Lymphocyte TNFRSF5 gene TNFSF5 gene Technology Testing Work antimicrobial diarrheal disease enteric infection enteric pathogen experimental study genetic approach in vivo insight lymphoid structures mouse model novel pathogen programs protective effect resistance mechanism response single cell sequencing

项目摘要

Project Summary The ability of recently activated T cells to express the cell surface molecule CD40L allows them to communicate with other immune and non-immune populations. This molecule is of particular importance in the gut to help control the parasitic infection caused by Cryptosporidium. Here we leverage a novel, natural mouse model of Cryptosporidium to dissect the impact of the CD40-CD40L interaction in T cell-mediated resistance to infection in the gut. In this model, WT mice (like humans) develop sterile immunity mediated by T cell production of IFN-γ, but mice that lack CD40L mice (like humans) do not resolve infection. In addition, treatment of chronically infected CD40L-deficient mice with soluble (s)CD40L results in rapid parasite clearance. We will test if protective effect of CD40L may be explained by either I. its ability to promote T cell responses essential for resistance and/or II. because CD40L directly activates EC to limit parasite growth. We are uniquely equipped to utilize parasite transgenesis, combined with sophisticated genetic approaches to define the key cellular interactions that allows CD40L to determine the outcome of an enteric infection.

项目概要最近激活的 T 细胞表达细胞表面分子 CD40L 的能力使它们能够该分子在与其他免疫和非免疫群体的交流中特别重要。肠道来帮助控制隐孢子虫引起的寄生虫感染在这里，我们利用一种新型的天然小鼠。隐孢子虫模型剖析 CD40-CD40L 相互作用对 T 细胞介导的耐药性的影响在该模型中，WT 小鼠（像人类一样）产生由 T 细胞介导的无菌免疫。 IFN-γ 的产生，但缺乏 CD40L 的小鼠（如人类）不能解决感染。用可溶性 (s)CD40L 治疗慢性感染的 CD40L 缺陷小鼠会导致快速寄生虫我们将测试 CD40L 的保护作用是否可以通过其促进 T 细胞的能力来解释。抗性和/或 II 反应至关重要，因为 CD40L 直接激活 EC 以限制寄生虫生长。具有独特的能力，可以利用寄生虫转基因，并结合复杂的遗传方法定义允许 CD40L 确定肠道感染结果的关键细胞相互作用。