The role of CD40L in resistance to 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 与其他免疫和非免疫人群进行交流。该分子在 肠道有助于控制隐孢子虫引起的寄生虫感染。在这里，我们利用了一种新颖的、天然的鼠标 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 肠道感染。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）无法解决感染问题。此外， 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 清关。我们将测试 CD40L 的保护作用是否可以通过 I. 它促进 T 细胞的能力来解释 对抵抗和/或 II 至关重要的反应。因为CD40L直接激活EC来限制寄生虫的生长。我们 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。

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.