Neutrophil Dependent Immunity to Strongyloides Stercoralis

对粪类圆线虫的中性粒细胞依赖性免疫

• 批准号: 7885776
• 负责人: DAVID ABRAHAM
• 金额: $ 38.63万
• 依托单位: THOMAS JEFFERSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7885776
• 关键词: Adherence; Antibodies; Antibody Formation; B-Lymphocytes; Behavior; Cells; Complement; Data; Diffusion; Disease; Future; Goals; Grant; Health; Helminths; Human; Immune; Immune response; Immunity; Immunoglobulin G; In Vitro; Infection; Infection Control; Knowledge; Larva; Life Cycle Stages; Mediating; Methods; Molecular; Mus; Nematoda; Parasites; Parasitic infection; Rattus; Role; Strongyloides ratti; Strongyloides stercoralis; Strongyloidiasis; Surface; T-Lymphocyte; Tissues; eosinophil; extracellular; granulocyte; in vivo; killings; macrophage; monocyte; mouse model; neutrophil; novel vaccines; pathogen; response

The goal of these studies is to determine the mechanisms utilized by mouse neutrophils to control helminth infections. Previous studies have demonstrated that neutrophils are required for killing larval Strongyloides stercoralis in na�ve and immunized mice. The proposed studies will determine the molecular mechanisms used by neutrophils to kill the worm and methods used by antibody to accelerate parasite killing by neutrophils. These studies will provide an in depth analysis of how neutrophils control extracellular pathogens, and the findings will have applicability to our understanding of granulocyte control of bacterial, fungal and parasitic infections. The objective of Specific Aim 1 is to develop a comprehensive, sequential understanding of how mouse neutrophils kill the worms in the absence of antibody. It is clear from our previous studies that optimal neutrophil killing of the larvae results only after stimulation of the neutrophils with factors derived from macrophages and vice versa. We will decipher how neutrophils interact with macrophage derived factors to kill the parasites. The mechanisms and molecules used by the neutrophils to trap and then kill these non-phagocytosable pathogens will be determined. In Specific Aim 2 we will determine how larval killing by neutrophils is accelerated and amplified by the presence of parasite-specific antibody. It will be determined if the increase in efficiency of immune killing of parasites by neutrophils is dependent on direct interaction between antibody and neutrophils or by an effect of antibody on the behavior of the parasites promoting killing by neutrophils.

这些研究的目的是确定小鼠中性粒细胞控制蠕虫感染的机制。先前的研究已经证明，中性粒细胞是杀死幼稚和免疫小鼠中的粪类圆线虫幼虫所必需的。拟议的研究将确定中性粒细胞杀死蠕虫的分子机制和抗体加速中性粒细胞杀死寄生虫的方法。这些研究将深入分析中性粒细胞如何控制细胞外病原体，这些发现将适用于我们对细菌，真菌和寄生虫感染的粒细胞控制的理解。具体目标1的目的是建立一个全面的，连续的了解小鼠中性粒细胞如何杀死蠕虫在没有抗体的情况下。从我们以前的研究中可以清楚地看出，只有在用来自巨噬细胞的因子刺激中性粒细胞后，才能产生对幼虫的最佳中性粒细胞杀伤，反之亦然。我们将破译中性粒细胞如何与巨噬细胞衍生因子相互作用以杀死寄生虫。将确定中性粒细胞捕获并杀死这些不可吞噬病原体的机制和分子。在特定目标2中，我们将确定中性粒细胞如何通过寄生虫特异性抗体的存在加速和放大幼虫杀伤。将确定嗜中性粒细胞免疫杀死寄生虫的效率的增加是否依赖于抗体和嗜中性粒细胞之间的直接相互作用或抗体对促进嗜中性粒细胞杀死寄生虫的行为的影响。