Function of hemolymph plasma proteins in insect immune responses

昆虫有一个先天免疫系统，可以防止病原体的感染， 寄生虫本项目的总体目标是研究昆虫血淋巴血浆中的蛋白质 参与昆虫免疫的不同方面。这个实验室以前的工作 建立了鳞翅目昆虫，天蛾，作为一个模型系统，非常适合 血淋巴蛋白质复杂功能的生化表征。在我们的工作中， 在接下来的五年里，我们计划研究免疫的三个方面， 血浆蛋白(1)我们将描述血浆蛋白与肽聚糖的相互作用 来自触发丝氨酸蛋白酶活化的革兰氏阴性和革兰氏阳性细菌， 从而引发蛋白酶级联反应，导致酚氧化酶和Toll 通路(2)我们将研究血淋巴的氧化还原环境是如何调节的， 免疫反应，并测试免疫蛋白可能受巯基调节的假设 修改. (3)哺乳动物有很好的剥夺入侵的机制 微生物的铁;然而，免疫相关的铁扣留在昆虫仍然很差 明白我们将使用M。Sexta作为发现保守铁滞留的模型 昆虫的机制由此获得的基本生物化学知识 研究有望促进对蛋白酶级联调节的更好理解 昆虫血淋巴中有助于氧化调节的途径和分子 免疫力，并导致了解铁如何影响人类疾病的传播， 昆虫媒介。

Insects have an innate immune system that protects against infections by pathogens and parasites. The overall goal of this project is to investigate proteins in insect hemolymph plasma that participate in different aspects of insect immunity. Previous work from this laboratory has established the lepidopteran insect, Manduca sexta, as a model system well suited for biochemical characterization of the complex functions of hemolymph proteins. In our work over the next five years, we plan to investigate three aspects of immunity that are mediated by plasma proteins. (1) We will characterize interactions of plasma proteins with peptidoglycan from Gram-negative and Gram-positive bacteria that trigger activation of a serine protease, thereby initiating protease cascades that result in activation of phenoloxidase and the Toll pathway. (2) We will investigate how the redox environment of hemolymph is regulated during an immune response and test a hypothesis that immune proteins may be regulated by thiol modifications. (3) Mammals have well-characterized mechanisms for depriving invading microorganisms of iron; however, immune-related iron-withholding in insects is still poorly understood. We will use M. sexta as a model for discovering conserved iron-withholding mechanisms in insects. The fundamental biochemical knowledge gained as a result of this research is expected to stimulate better understanding of regulation of protease cascade pathways and molecules in insect hemolymph that contribute to oxidative modulation during immunity, and lead to understanding of how iron influences human disease transmission by insect vectors.