The role of CX3CR1+ CD4+ T cells during helminth infection

全世界有超过20亿人感染寄生蠕虫。它们会导致严重的发病率和死亡率 在世界的发展中地区，特别是在儿童中间。一种针对任何类型的人类的有效疫苗 蠕虫感染一直难以捉摸，部分原因是人们对如何诱导保护性 对这些寄生虫的免疫力。寄生蠕虫诱导一种由CD4TH2驱动的免疫反应。这 反应不仅对于驱除寄生虫是必要的，而且对于修复感染和 减轻慢性持续性导致的任何进一步的病理改变。开发一种有效的疫苗来预防 蠕虫可能需要仔细了解CD4记忆T细胞形成的机制和 功能。某些亚群的CD4和CD8 T细胞将表达趋化因子受体CX3CR1 炎症和感染。CD8T细胞上CX3CR1的表达有助于预测记忆表型 病毒感染。CX3CR1 CD4T细胞在蠕虫诱导的2型免疫应答中的作用 感染是完全未知的。我们最近发现CX3CR1的CD4T细胞聚集在 受蠕虫感染的组织，但不在引流的淋巴结内。在曼森血吸虫期间 在肉芽肿形成过程中，感染CX3CR1的CD4T细胞会在肝脏中积聚。在尼波斯特龙星期间 感染巴西里氏吸虫后，这些细胞会迅速聚集在肺部。这项提议的目标是进一步 通过两个特定的目标来表征这一群体的CD4T细胞的表型和功能。在 首先，我们将测试CX3CR1 CD4T细胞在蠕虫感染期间来自炎症组织的假设 感染可以在转运到脾后分化为T滤泡辅助细胞。在第二个目标中，我们将 确定CX3CR1 CD4T细胞是否有助于生发中心的形成、抗体反应和宿主 防止二次感染。总体而言，我们提出的研究将增加我们对 蠕虫感染小鼠组织中的CD4CX3CR1细胞，在2型免疫反应中。这 人们对T细胞群体知之甚少，可能对支持抗体反应、寄生虫很重要 驱逐、保护性免疫和组织修复。利用遗传命运图谱和条件耗竭 系统，我们可以彻底描述它们在蠕虫感染过程中的表型和功能。

Parasitic helminths infect over 2 billion people worldwide. They cause significant morbidity and mortality in developing areas of the world, especially among children. An effective vaccine against any type of human helminth infections has been elusive, partly because there is a poor understanding of how to induce protective immunity against these parasites. Parasitic helminths induce a CD4+ TH2 driven immune response. This response is necessary not only to expel the parasite, but also to repair tissue damage caused by infection and mitigate any further pathology resulting from chronic persistence. The development of an effective vaccine to helminths may require a meticulous understanding of the mechanism of CD4+ memory T cell formation and function. Certain subsets of CD4+ and CD8+ T cells will express the chemokine receptor CX3CR1 during inflammation and infection. CX3CR1 expression on CD8+ T cells can help predict memory phenotypes during viral infections. The role of CX3CR1+ CD4+ T cells during type-2 immune responses induced by helminth infection is completely unknown. We have recently found that CX3CR1+ CD4+ T cells accumulate in the tissues affected by helminth infections, but not in the draining lymph nodes. During Schistosoma mansoni infection CX3CR1+ CD4+ T cells accumulate in the liver during granuloma formation. During Nippostrongylus brasiliensis infection these cells rapidly accumulate in the lungs. The goal of this proposal is to further characterize the phenotype and function of this population of CD4+ T cells, through two specific aims. In the first Aim, we will test the hypothesis that CX3CR1+ CD4+ T cells from inflamed tissues during helminth infection can differentiate into T follicular helper cells after trafficking to the spleen. In the second Aim, we will determine if CX3CR1+ CD4+ T cells contribute to germinal center formation, antibody responses and host protection against secondary infection. Overall, the study we propose will increase our understanding of CD4+CX3CR1+ cells in the tissues of helminth infected mice, during a type-2 immune response. This population of T cells is poorly understood and may be important for supporting antibody responses, parasite expulsion, protective immunity and tissue repair. Utilizing genetic fate-mapping and conditional depletion systems, we can thoroughly characterize their phenotype and function during helminth infections.