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

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
批准号:
7922655
负责人:
Andre Bafica
金额:
$5.17万
依托单位国家:
美国
项目类别:
财政年份:
2009
资助国家:
美国
项目状态:
已结题
起止时间:
2009-09-01 至 2015-08-31
关键词:
AgonistAntibiotic TherapyAntigen-Presenting CellsAntitubercular AgentsBacteriaBindingBiochemicalBioinformaticsBiological MarkersBlocking AntibodiesBrazilC Type Lectin ReceptorsC-Type LectinsCD209 geneCD80 geneCell CommunicationCell Culture TechniquesCell LineCell physiologyCellsCitiesCoculture TechniquesCommunicable DiseasesConfocal MicroscopyCytokine GeneCytometryDataData AnalysesDatabasesDendritic CellsDevelopmentDiagnosticDiseaseEnzyme-Linked Immunosorbent AssayErythrocytesExposure toFamilyFlow CytometryGene ExpressionGenesGenus MycobacteriumGoalsGreen Fluorescent ProteinsHealthHost resistanceHumanImmune responseImmune systemImmunityImmunoglobulin GImmunologic ReceptorsImmunotherapyIn VitroInfectionInflammation MediatorsInflammatoryInterferon Type IIInterleukin-10Interleukin-12Interleukin-17Interleukin-6KnowledgeLectinLung diseasesMHC Class II GenesMacrophage-1 AntigenMeasuresMembraneModelingMonoclonal AntibodiesMusMycobacterium smegmatisMycobacterium tuberculosisOutcomeOutcome StudyPathogenesisPathway interactionsPatient MonitoringPatientsPatternPeripheral Blood Mononuclear CellPhagocytosisPlayPreparationProcessProductionProtein Binding DomainProteinsPublishingReagentRecombinantsResearchRicinRoleScreening procedureSerumSurfaceSystemT-Cell ProliferationT-LymphocyteTLR2 geneTLR3 geneTLR4 geneTLR7 geneTNF geneTNFRSF5 geneTestingTimeToll-like receptorsTuberculosisVirulenceWorkbasechemotherapycohortcytokinedectin 1glucan phosphateimmunoprophylaxisimprovedin vivointerestinterleukin-23laminaranmacrophagemonocytemycobacterialneutralizing antibodynovelpathogenprotein protein interactionreceptorreceptor expressionresearch studyresponsestemsugartooltuberculosis treatmentuptake

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中文摘要
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描述(由申请人提供):M.结核分枝杆菌13 kDa凝集素调节人类免疫应答研究结核分枝杆菌的新蛋白质可能是改进结核病诊断工具、治疗和免疫预防的关键步骤,结核病是全球最流行的传染病之一。我们从M.发现结核病凝集红细胞并诱导巨噬细胞表达细胞因子。此外,活动性结核病患者的血清中含有高水平的抗这种凝集素的IgG。在本提案中,我们的目标是表征13 KDa Mtb凝集素对人类免疫应答的作用。本研究的具体目的是:1)表征13 KDa Mtb凝集素引起的先天免疫应答模式; 2)确定参与识别13 KDa Mtb凝集素的人APC上表达的先天受体; 3)研究13 KDa Mtb凝集素在M.通过人APC检测结核病患者的特异性体液和细胞免疫应答,以及4)在抗生素治疗之前和之后检测结核病患者中针对13 KDa Mtb凝集素的特异性体液和细胞免疫应答。我们的长期目标是确定13 KDa Mtb蓖麻毒素样凝集素是否在调节人类对TB的免疫应答中起作用,重点是它在控制APC功能中的可能活性。这些研究对于揭示结核病免疫治疗的新靶点具有重要意义。公共卫生相关性:M。结核病13 kDa凝集素调节人类免疫反应项目叙述该项目的开发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结核病免疫治疗的新靶点以及疾病生物标志物非常重要。
英文摘要
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.
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Mechanisms by which M. tuberculosis 13KDa lectin modulates human immune responses
Mechanisms by which M. tuberculosis 13KDa lectin modulates human immune responses
Mechanisms by which M. tuberculosis 13KDa lectin modulates human immune responses
Mechanisms by which M. tuberculosis 13KDa lectin modulates human immune responses
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