Gr-1+ cells and the response to nematode parasites

Gr-1 细胞和对线虫寄生虫的反应

• 批准号: 7762243
• 负责人: William Clark Gause
• 金额: $ 36.66万
• 依托单位: UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-15 至 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7762243
• 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; Gene Expression; Host resistance; Hour; Immigration; Immune response; 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; adaptive immunity; chemokine; chemokine receptor; cytokine; eosinophil; granulocyte; in vivo; lymph nodes; macrophage; migration; monocyte; neutrophil; novel; response; therapy development; tumor

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.

辅助性T细胞2(Th2)效应细胞可通过Th2细胞因子的产生介导对蠕虫的抵抗 寄生虫感染。了解导致它们分化的细胞和分子相互作用 因此对开发促进宿主保护性免疫的疗法和疫苗很重要 回应。我们已经开始研究最初在感染老鼠后产生的先天反应。 用线虫寄生来识别在促进适应能力方面可能重要的细胞群或信号 免疫导致产生IL-4的Th2细胞的发育。全球基因表达分析 在寄生虫感染后不久，引流淋巴结中的趋化因子显著增加，包括 MCP-1和CXCR3配体。这两种趋化因子都知道如何募集单核细胞和粒细胞。GR-1是一种 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 在接种肠道后4小时和16小时，结节中Gr-1+细胞显著增加 线虫寄生虫，巴西线虫。抗GR-1抗体治疗后淋巴液显著增加 巴西奈瑟氏菌接种后18h结节干扰素-v的表达及IL-4表达和宿主的减少 接种后7d观察到抗性。在建议的研究中，我们会探讨 GR-1+细胞对体内Th2效应细胞发育的促进作用具体地说，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 处于免疫反应早期阶段的节点对巴西新城疫病毒。我们还将阐明其机制。 Gr-1+细胞如何抑制干扰素-γ的升高并促进Th2细胞的发育从而导致宿主抵抗 原位检测Gr-1+细胞与发育中的Th2细胞的相互作用。最后，我们将讨论两种寄生虫 模型中Gr-1+细胞在发育过程中的作用 主要和内存响应。

项目成果

Antibodies trap tissue migrating helminth larvae and prevent tissue damage by driving IL-4Rα-independent alternative differentiation of macrophages.

• DOI: 10.1371/journal.ppat.1003771
• 发表时间: 2013
• 期刊: PLoS pathogens
• 影响因子: 6.7
• 作者: Esser-von Bieren J;Mosconi I;Guiet R;Piersgilli A;Volpe B;Chen F;Gause WC;Seitz A;Verbeek JS;Harris NL
• 通讯作者: Harris NL

Micrometer-sized titanium particles can induce potent Th2-type responses through TLR4-independent pathways.

• DOI: 10.4049/jimmunol.1101392
• 发表时间: 2011-12-15
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Mishra PK;Wu W;Rozo C;Hallab NJ;Benevenia J;Gause WC
• 通讯作者: Gause WC