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Novel Innate Receptor for the Fungal PAMP chitin

真菌 PAMP 几丁质的新型先天受体

基本信息

批准号：
8839039
负责人：
LIWU LI
金额：
$ 23.37万
依托单位：
VIRGINIA POLYTECHNIC INST AND ST UNIV
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-05-18 至 2017-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8839039
关键词：
Acetylglucosamine Age Alkalies Allergens Allergic Allergic Disease Allergic rhinitis Alternaria Animal Model Aspergillus fumigatus Asthma Automobile Driving Binding Biochemical Breathing CD4 Positive T Lymphocytes Calorimetry Carbohydrates Cell Wall Cell membrane Cells Cessation of life Child Childhood Chitin Chronic Clinical Collaborations Complex Country Data Dendritic Cells Developed Countries Development Disease Employee Strikes Environmental Risk Factor Eosinophilia Epithelial Cells Equilibrium Event Exhibits Exposure to Extrinsic asthma Fungal Antigens Genes Glucans Goals Healthcare Systems Human Hypersensitivity IRAK1 gene IgE Immune Immune response Immune system Immunity In Vitro Individual Inflammation Inflammatory Inflammatory Response Investigation Kinetics Knowledge Lead Ligands Link Lung Mucous body substance Mus Natural Immunity Nature Obstruction Parasites Pathogenesis Pathway interactions Patients Peptidoglycan Phase Phenotype Phosphotransferases Play Polymers Population Prevalence Prevention Prevention strategy Process Production Proteins Public Health Recombinants Recurrence Reproduction spores Research Rhinitis Role Serum Signal Transduction Site Small Interfering RNA Specificity Testing Titrations Translating United States United States National Institutes of Health Variant Work adaptive immunity airway hyperresponsiveness airway inflammation airway remodeling allergic airway disease allergic airway inflammation allergic response clinical practice cytokine dectin 1 design effective therapy experience falls fungus galactomannan human IRAK1 protein in vivo insight mouse model mutant novel novel therapeutic intervention pathogen pressure public health relevance receptor response screening

项目摘要

DESCRIPTION (provided by applicant): The inflammatory airway response in allergic asthma may be the result of immune cells that are dysregulated towards environmental factors such as airborne fungi. The long-term goal of this project is to better understand the pathophysiological mechanisms of Th2-type (allergic) airway inflammation. Exposure to the fungus, Alternaria, has long been implicated in the development and exacerbation of allergic airway disorders such as rhinitis, atopic asthma, and CRS. After intranasal exposure to Alternaria spores, antigens, and fungal cell wall polymers such as chitin, naive mice exhibit marked eosinophilic airway inflammation, enhanced Th2 responses, and airway hyperreactivity. Despite the well-documented clinical importance of Alternaria in the development, onset, and exacerbation of allergic airway diseases, little knowledge exists about the role of individual fungal products/components in theses pathological states. The importance of the fungal cell wall polymer chitin has been explored to some extent in the context of inflammation and has been shown to drive immune responses favoring the development of allergic disease. We have discovered a novel receptor candidate for chitin expressed in lung epithelial cells. In this exploratory project we will further our understanding of how chitin binds to this receptor and begin to elucidate the role of this receptor candidate in the context of innate immunity and allergic inflammatory responses using lung epithelial cells and mouse models. Execution of this project will lead to a better understanding of the mechanisms of persistent and recurrent airway inflammation and may lead to the development of more specific, effective therapies and prevention strategies.

描述（由申请人提供）：过敏性哮喘中的气道炎症反应可能是免疫细胞对环境因素（如空气中的真菌）失调的结果。该项目的长期目标是更好地了解Th 2型（过敏性）气道炎症的病理生理机制。暴露于真菌，链格孢属，长期以来一直涉及过敏性气道疾病，如鼻炎，特应性哮喘和CRS的发展和恶化。在鼻内暴露于链格孢属孢子、抗原和真菌细胞壁聚合物（如几丁质）后，幼稚小鼠表现出显著的嗜酸性气道炎症、增强的Th 2应答和气道高反应性。尽管链格孢属在过敏性气道疾病的发展、发作和恶化中的临床重要性已被充分证明，但关于个体真菌产物/组分在这些病理状态中的作用的知识却很少。真菌细胞壁聚合物几丁质的重要性已经在炎症的背景下在一定程度上被探索，并且已经显示出驱动有利于过敏性疾病发展的免疫应答。我们已经发现了一种新的候选受体几丁质表达在肺上皮细胞。在这个探索性的项目中，我们将进一步了解几丁质如何结合到这种受体，并开始阐明这种受体候选人在先天免疫和过敏性炎症反应的背景下，使用肺上皮细胞和小鼠模型的作用。该项目的执行将导致更好地了解持续性和复发性气道炎症的机制，并可能导致更具体，有效的治疗和预防策略的发展。