Neutrophil Dependent Immunity to Strongyloides Stercoralis

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。先前的研究表明，中性粒细胞是杀死幼年和免疫小鼠体内的粪类圆线虫幼虫所必需的。拟开展的研究将确定中性粒细胞杀死线虫的分子机制和抗体加速中性粒细胞杀死寄生虫的方法。这些研究将提供中性粒细胞如何控制细胞外病原体的深入分析，并且这些发现将适用于我们对粒细胞控制细菌，真菌和寄生虫感染的理解。Specific Aim 1的目的是对小鼠中性粒细胞如何在缺乏抗体的情况下杀死蠕虫进行全面、有序的了解。从我们之前的研究中可以清楚地看出，只有在巨噬细胞来源的因子刺激中性粒细胞后，才能达到最佳的中性粒细胞杀伤幼虫，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。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将被确定。在特异性目标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扩增幼虫。中性粒细胞对寄生虫免疫杀灭效率的提高取决于抗体与中性粒细胞之间的直接相互作用，还是取决于抗体对促进中性粒细胞杀伤的寄生虫行为的影响，这将被确定。

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.