Function of hemolymph plasma proteins in insect immune responses

昆虫有一种天生的免疫系统，可以保护自己免受病原体和 寄生虫。这个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是 建立了鳞翅目昆虫Manduca sexta，作为适合于 血淋巴蛋白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，这三个方面是由 血浆蛋白。(1)我们将研究血浆蛋白与肽聚糖的相互作用 从革兰氏阴性和革兰氏阳性细菌中引发丝氨酸蛋白酶的激活， 从而启动蛋白酶级联反应，导致酚氧化酶和Toll的激活 路径。(2)我们将研究血淋巴的氧化还原环境是如何在 一种免疫反应，并检验免疫蛋白可能受硫醇调节的假说 修改。(3)哺乳动物有各具特色的剥夺入侵的机制 铁的微生物；然而，昆虫中与免疫相关的铁抑制作用仍然很差 明白了。我们将使用六分枝杆菌作为发现保守的铁保留的模型。 昆虫的机制。由此获得的基础生物化学知识 研究有望促使人们更好地理解蛋白水解酶的级联调控 昆虫血淋巴中参与氧化调节的途径和分子 免疫力，并导致理解铁是如何影响人类疾病传播的 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.