Mechanisms by which M. tuberculosis 13KDa lectin modulates human immune responses

结核分枝杆菌 13KDa 凝集素调节人体免疫反应的机制

基本信息

批准号：
7688816
负责人：
Andre Bafica
金额：
$ 5.28万
依托单位：
FEDERAL UNIVERSITY OF SANTA CATARINA
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-01 至 2015-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7688816
关键词：
Agonist Antibiotic Therapy Antigen-Presenting Cells Antitubercular Agents Bacteria Binding Biochemical Bioinformatics Biological Markers Blocking Antibodies Brazil C Type Lectin Receptors C-Type Lectins CD209 gene CD80 gene Cell Communication Cell Culture Techniques Cell Line Cell physiology Cells Cities Coculture Techniques Communicable Diseases Confocal Microscopy Cytokine Gene Cytometry Data Data Analyses Databases Dendritic Cells Development Diagnostic Disease Enzyme-Linked Immunosorbent Assay Erythrocytes Exposure to Family Flow Cytometry Gene Expression Genes Genus Mycobacterium Goals Green Fluorescent Proteins Health Host resistance Human Immune response Immune system Immunity Immunoglobulin G Immunologic Receptors Immunotherapy In Vitro Infection Inflammation Mediators Inflammatory Interferon Type II Interleukin-10 Interleukin-17 Interleukin-6 Knowledge Lectin Lung diseases MHC Class II Genes Macrophage-1 Antigen Measures Membrane Modeling Monoclonal Antibodies Mus Mycobacterium smegmatis Mycobacterium tuberculosis Outcome Outcome Study Pathogenesis Pathway interactions Patient Monitoring Patients Pattern Peripheral Blood Mononuclear Cell Phagocytosis Play Preparation Process Production Protein Binding Domain Proteins Publishing Reagent Recombinants Research Ricin Role Screening procedure Serum Surface System T-Cell Proliferation T-Lymphocyte TLR2 gene TLR3 gene TLR4 gene TNF gene TNFRSF5 gene Testing Time Toll-like receptors Tuberculosis Virulence Work base chemotherapy cohort cytokine dectin 1 glucan phosphate immunoprophylaxis improved in vivo interest interleukin-23 laminaran macrophage monocyte mycobacterial neutralizing antibody novel pathogen protein protein interaction public health relevance receptor receptor expression research study response stem sugar tool tuberculosis treatment uptake

项目摘要

DESCRIPTION (provided by applicant): Mechanisms by which M. tuberculosis 13 kDa lectin modulates human immune responses Project Summary Study of novel proteins from Mycobacterium tuberculosis may be a critical step for improving diagnostic tools, therapies and immunoprophylaxis against tuberculosis (TB), one of the most prevalent infectious diseases wordwide. We have identified a 13 KDa ricin-like lectin from M. tuberculosis that was found to agglutinate red blood cells and induce cytokine expression by macrophages. Moreover, serum from active tuberculosis patients contained high levels of IgG against this lectin. In the present proposal, we aim to characterize the role of 13 KDa Mtb lectin on human immune responses. The specific aims of the study are to 1) characterize the innate immune response profile elicited by the 13 KDa Mtb lectin; 2) determine innate receptor(s) expressed on human APC involved in the recognition of 13 KDa Mtb lectin; 3) investigate the role of 13 KDa Mtb lectin in the infection/phagocytosis process of M. tuberculosis by human APC and 4) examine specific humoral and cellular immune responses against 13 KDa Mtb lectin in TB patients before and after antibiotic treatment. Our long-term goal is to determine whether 13 KDa Mtb ricin-like lectin plays a role in regulating human immune responses to TB focusing on it possible activity in controlling APC function. These studies could be important in revealing a new target for immunotherapy of tuberculosis. PUBLIC HEALTH RELEVANCE: Mechanisms by which M. tuberculosis 13 kDa lectin modulates human immune responses Project Narrative Development of this project may impact human health because understanding of interactions between Mycobacteria and human cells could be important in revealing novel targets for immunotherapy of tuberculosis as well as disease biomarkers.

描述（由申请人提供）：结核分枝杆菌13 KDA凝集素调节的机制调节人类免疫反应的项目摘要研究对结核分枝杆菌的新蛋白质的新蛋白质可能是改善诊断工具，治疗工具，治疗和免疫蛋白毒素（TB）的关键步骤（TB）（TB），这是最先进的疾病，其中一项是疾病的疾病。我们已经从结核分枝杆菌中鉴定出13 kDa ricin样凝集素，发现巨噬细胞会凝结红细胞并诱导细胞因子的表达。此外，活性结核病患者的血清含有高水平的IgG针对该凝集素。在本提案中，我们旨在表征13 kDa MTB凝集素对人免疫反应的作用。该研究的具体目的是1）表征13 kDa MTB凝集素引起的先天免疫反应曲线； 2）确定与识别13 kDa MTB凝集素有关的人APC表示的先天受体； 3）研究人APC的13 kDa MTB凝集素在结核分枝杆菌的感染/吞噬作用中，4）检查抗生素治疗前后的TB患者中针对13 kDa MTB凝集素的特定体液和细胞免疫反应。我们的长期目标是确定13 kDa mtb ricin样凝集素是否在调节人类免疫反应中对TB的免疫反应起着作用，重点是控制APC功能。这些研究对于揭示结核病免疫疗法的新靶标可能很重要。公共卫生相关性：结核分枝杆菌13 kDa凝集素调节人类免疫反应的机制可能会影响人类健康，因为了解分枝杆菌和人类细胞之间的相互作用对于揭示揭示结核病免疫疗法的新目标可能很重要。