The role of CD40L in resistance to enteric infection

项目摘要 最近活化的T细胞表达细胞表面分子CD 40 L的能力使它们能够 与其他免疫和非免疫群体交流。这种分子在生物学中具有特别重要的意义。 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的，自然的老鼠 隐孢子虫模型，以剖析CD 40-CD 40 L相互作用在T细胞介导的对 肠道感染在该模型中，WT小鼠（像人一样）产生由T细胞介导的无菌免疫。 但是缺乏CD 40 L的小鼠（如人类）不能解决感染。此外，本发明还提供了一种方法， 用可溶性CD 40 L治疗慢性感染的CD 40 L缺陷小鼠， 间隙我们将检测CD 40 L的保护作用是否可以用I.其促进T细胞增殖能力 对于抗性和/或II.因为CD 40 L直接激活EC以限制寄生虫生长。我们 利用寄生虫转基因的独特装备，结合复杂的遗传方法， 定义关键的细胞相互作用，使CD 40 L决定肠道感染的结果。

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.