Gr-1+ cells and the response to nematode parasites

Gr-1 细胞和对线虫寄生虫的反应

基本信息

批准号：
7373545
负责人：
William Clark Gause
金额：
$ 37.03万
依托单位：
UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-03-15 至 2011-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7373545
关键词：
Address Adjuvant Antibodies Binding CCL2 gene CD4 Positive T Lymphocytes CXCL10 gene CXCR3 gene Cell Communication Cell Differentiation process Cell surface Cells Cervical lymph node group Characteristics Chemotaxis Communicable Diseases Dendritic Cells Development Effector Cell Elevation Gene Expression Host resistance Hour Immigration Immune response Immunity In Situ Individual Infection Interleukin-4 Intestines Lead Ligands Lymphoid Lymphoid Tissue Mediating Memory Modeling Mus Myeloid Cells Nematoda Organ Parasites Peripheral Play Population Population Heterogeneity Production Recruitment Activity Resistance Role Secondary to Signal Transduction Site Specificity Staging Staining method Stains T-Lymphocyte Tumor stage Up-Regulation Vaccine Therapy chemokine chemokine receptor cytokine day eosinophil granulocyte in vivo lymph nodes macrophage migration monocyte neutrophil novel response tumor

项目摘要

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.

辅助 T 2 (Th2) 效应细胞通过 Th2 细胞因子的产生，可以介导对蠕虫的抵抗力寄生虫感染。了解导致细胞分化的细胞和分子相互作用是因此对于开发促进宿主保护性免疫的疗法和疫苗非常重要回应。我们已经开始检查小鼠感染后最初出现的先天反应与线虫寄生虫一起识别对促进适应性可能重要的细胞群或信号导致产生 IL-4 的 Th2 细胞发育的免疫。全局基因表达分析寄生虫感染后不久，引流淋巴结显示趋化因子显着增加，包括 MCP-1 和 CXCR3 配体。已知这两种趋化因子都会募集单核细胞和粒细胞。 Gr-1 是这些细胞群和浆细胞样树突状细胞共有的细胞表面标记。引流淋巴液接种肠道后 4 小时和 16 小时，节点中 Gr-1+ 细胞显着增加线虫寄生虫，N. brasiliensis。抗 GR-1 抗体治疗导致淋巴明显增加巴西猪笼草接种后 18 小时节点 IFN-v 表达以及 IL-4 表达和宿主降低接种后7天观察耐药情况。在拟议的研究中，我们将研究 Gr-1+细胞在体内促进Th2效应细胞的发育。具体来说，我们建议确定介导 Gr-1+ 细胞募集至外周淋巴的趋化因子/趋化因子受体对巴西奈瑟菌免疫反应早期阶段的节点。我们还将阐明其机制 Gr-1+ 细胞如何抑制 IFN-y 升高并促进 Th2 细胞发育，从而导致宿主抵抗原位检查 Gr-1+ 细胞与发育中的 Th2 细胞的相互作用。最后，我们将讨论两个寄生虫模型，N. brasiliensis 和 H. polygyrus，Gr-1+ 细胞在宿主保护性发育中的作用主要反应和记忆反应。