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Mechanism of Mycoplasma-Induced Mast Cell Il-4 Synthesis

支原体诱导肥大细胞 IL-4 合成的机制

基本信息

批准号：
7392363
负责人：
THOMAS PRESCOTT ATKINSON
金额：
$ 45.56万
依托单位：
NATIONAL JEWISH HEALTH
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-04-01 至 2009-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7392363
关键词：
Ablation Acute Adhesives Adoptive Transfer Adult Affect Allergens Allergic Animal Model Animals Antibiotics Antigens Asthma Attenuated Bacteria Bacterial Adhesins Basic Science Biological Assay Biopsy Blocking Antibodies Bronchoalveolar Lavage Fluid CD4 Positive T Lymphocytes Caffeine Cell Count Cell Line Cell surface Cells Chronic Clinical Coculture Techniques Collaborations Complement Condition Cytokine Activation DNA-Directed DNA Polymerase Data Development Diagnosis Educational process of instructing Epidemic Escherichia coli Extracellular Domain Extrinsic asthma Funding Gastritis Glycoproteins Goals Helicobacter Infections Helicobacter pylori Helper-Inducer T-Lymphocyte Histology Human Hypersensitivity IgE Immune Immune response Immunization In Vitro Individual Infection Inflammation Inflammatory Interleukin-4 Laboratories Life Ligands Lipoproteins Lung Lung diseases Lymphocyte Mediator of activation protein Medical Students Messenger RNA Microbiology Modeling Molecular Mus Mutagenesis Mutant Strains Mice Mycoplasma Mycoplasma Infections Mycoplasma pneumoniae Neurokinin A Neuropeptides Nose Numbers Organism Pathogenesis Pathology Peptic Ulcer Pharmaceutical Preparations Phenotype Pneumonia Polymerase Chain Reaction Polypropylenes Polystyrenes Population Predisposition Principal Investigator Production Program Research Project Grants Proteins Pulmonary Surfactant-Associated Protein D Range Recombinants Research Research Personnel Respiratory Tract Infections Role Sampling Serologic tests Signal Transduction Stomach Carcinoma Structure of parenchyma of lung Substance P Surface Symptoms T-Lymphocyte TNF gene Testing Time Type A Personality Vaccines Work airway hyperresponsiveness airway obstruction base cell type cytokine design flasks interleukin-4 Stat mast cell member microbial morphometry mouse model mutant pathogen polypeptide prevent programs pulmonary function reconstitution research study response tissue culture

项目摘要

The overall goals of this project are to define innate and adaptive immune mechanisms by which Mycoplasma pneumoniae contributes to the development of chronic airway hyperreactivity and inflammation, focusing on the role of mast cells. Specific Aim 1: To clone and express the P1 adhesin of M. pneumoniae in E. coli and to produce a mutant M. pneumoniae strain deficient in that molecule. The P1 adhesin or select fragments involved in the mast cell IL-4 response will be cloned and expressed in E. coli. Using transposon mutagenesis, a P1-deficient strain of M. pneumoniae will be produced for use in mast cell stimulation experiments and the mouse model of infection. Specific Aim 2: To identify and characterize surface molecules on mast cells that are essential for induction of IL-4 production by P1 glycoprotein, examine modulating effects of other molecules in the pulmonary microenvironment, validate the effects observed using human mast cells, and characterize the effects of knockdown of expression of specific molecules involved in the M. pneumoniae cytokine response in mast cell lines. Target molecules for M. pneumoniae-induced mast cell cytokine production will be identified and characterized and the effects of mutational deletion examined, modulating effects of mediators in the pulmonary microenvironment will be analyzed, and effects of M. pneumoniae in a new human mast cell line will be studied. Specific Aim 3: To determine if respiratory tract infection by M. pneumoniae induces the recruitment to the airways of TH2 CD4 + lymphocytes, and to determine if this occurs using a mechanism that is dependent on mast cell-derived IL-4 or other mast cell products. The ability of M. pneumoniae to cooperate in the mast cell-induced recruitment of TH2 cells to the lungs and airways will be studied using adoptive transfer of antigen specific T cells. Specific Aim 4: To characterize the effects of infection in a mouse model under conditions in which interactions between M. pneumoniae and mast cells have been abrogated or in which mast cell IL-4 production is prevented. P1 deficient strain(s) of M. pneumoniae will be tested in mice for effects on airway hyperreactivity in a chronic infection model. The role of target molecules on the mast cells for M. pneumoniae-induced cytokine production will be studied in mutant strains of mice.

该项目的总体目标是确定肺炎支原体促进慢性气道高反应性和炎症发展的先天和适应性免疫机制，重点关注肥大细胞的作用。