Gr-1+ cells and the response to nematode parasites

辅助性T细胞2（Th 2）效应细胞，通过Th 2细胞因子的产生，可以介导对蠕虫的抗性， 寄生虫感染了解导致其分化的细胞和分子相互作用是 因此对于促进宿主保护性免疫的疗法和疫苗的开发是重要的。 应答我们已经开始研究小鼠感染后最初产生的先天反应 与线虫寄生虫，以确定细胞群或信号，可能是重要的，在促进适应性 导致产生IL-4的Th 2细胞发育的免疫。全球基因表达分析 寄生虫感染后不久的引流淋巴结显示趋化因子明显增加，包括 MCP-1和CXCR 3配体。这两种趋化因子都可以募集单核细胞和粒细胞。Gr-1是一个 这些细胞群以及浆细胞样树突细胞共有的细胞表面标志物。引流淋巴 在接种肠毒素后4和16小时，淋巴结中Gr-1+细胞明显增加， 线虫寄生虫，N.巴西的。用抗GR-1抗体治疗引起淋巴细胞的显著增加， 在N.巴西曲霉接种并降低IL-4表达和宿主 在接种后7天观察到抗性。在建议的研究中，我们会研究 Gr-1+细胞促进体内Th 2效应细胞的发育。具体而言，我们建议确定 趋化因子/趋化因子受体介导Gr-1+细胞向外周淋巴的募集 在对N的免疫反应的早期阶段的节点。巴西的。我们还将阐明 Gr-1+细胞如何抑制IFN-γ升高并促进Th 2细胞发育，从而导致宿主抗性 原位检测Gr-1+细胞与发育中的Th 2细胞的相互作用。最后，我们将在两个寄生虫解决 models，N. brasiliensis和H.多回，Gr-1+细胞在宿主保护性发育中的作用 主要和内存响应。

T helper 2 (Th2)effector cells, through Th2 cytokine production, can mediate resistance to helminthic parasite infection. Understanding the cell and molecular interactions that lead to their differentiation is therefore important for the development of therapies and vaccines that promote host protective immune responses. We have begun to examine the innate response that initially develops following infection of mice with nematode parasites to identify cell populations or signals that may be important in promoting adaptive immunity that leads to the developing of IL-4producing Th2 cells. Global gene expression analyses of draining lymph nodes shortly after parasite infection showed pronounced increases in chemokines, including MCP-1 and CXCR3 ligands. Both chemokines are kn ow to recruit monocytes and granulocytes. Gr-1 is a cell surface marker shared by these cell populations and also plasmacytoid dendritic cells. Draining lymph nodes showed pronounced increases in Gr-1+ cells at 4 and 16 hours after inoculation with the intestinal nematode parasite, N. brasiliensis. Treatment with anti-GR-1 antibody caused marked increases in lymph node IFN-v expression at 18 hours after N. brasiliensis inoculation and decreased IL-4 expression and host resistance was observed at 7 days after inoculation. In the proposed studies, we will examine the function of Gr-1+ cells in promoting the development of Th2 effector cells in vivo. Specifically, we propose to identify the chemokine/chemokine receptors that mediate the recruitment of Gr-1+ cells to the peripheral lymph nodes at early stages of the immune response to N. brasiliensis. We will also elucidate the mechanism of how Gr-1+ cells suppress IFN-y elevations and promote Th2 cell development leading to host resistance by examining Gr-1+ cell interactions with developing Th2 cells in situ. Finally, we will address in two parasite models, N. brasiliensis and H. polygyrus, the role of Gr-1+ cells in the development of the host protective primary and memory response.