Function of hemolymph plasma proteins in insect immune responses

血淋巴血浆蛋白在昆虫免疫反应中的功能

• 批准号: 10728371
• 负责人: Michael R Kanost
• 金额: $ 2.72万
• 依托单位: KANSAS STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2026-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10728371
• 关键词: Affect; Arthropods; Biochemical; Biological Models; Complex; Disease Vectors; Environment; Evolution; Future; Goals; Gram-Positive Bacteria; Hemolymph; Immune; Immune response; Immunity; Immunologic Tests; Infection; Innate Immune Response; Innate Immune System; Insect Vectors; Insecta; Invaded; Investigation; Iron; Knowledge; Laboratories; Mammals; Manduca sexta; Mediating; Modeling; Modification; Monophenol Monooxygenase; Oxidation-Reduction; Parasites; Pathway interactions; Peptide Hydrolases; Peptidoglycan; Plasma; Plasma Proteins; Proteins; Regulation; Research; Serine Protease; Sulfhydryl Compounds; Work; disease transmission; human disease; innate immune mechanisms; microorganism; pathogen; transmission process

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.

昆虫具有先天免疫系统，可以防止病原体感染和 寄生虫。该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。该实验室之前的工作 建立了鳞翅目昆虫 Manduca sexta 作为非常适合的模型系统 血淋巴蛋白复杂功能的生化特征。在我们的工作中 未来五年，我们计划研究免疫介导的三个方面 血浆蛋白。 (1) 我们将表征血浆蛋白与肽聚糖的相互作用 来自触发丝氨酸蛋白酶激活的革兰氏阴性和革兰氏阳性细菌， 从而启动蛋白酶级联，导致酚氧化酶和 Toll 的激活 途径。 (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硫醇调节的假设 修改。 (3) 哺乳动物具有明显的剥夺入侵的机制 铁微生物；然而，昆虫中与免疫相关的铁保留仍然很差 明白了。我们将使用 M. sexta 作为发现保守铁保留的模型 昆虫的机制。由此获得的基本生化知识 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，并有助于了解铁如何影响人类疾病传播 昆虫载体。