Immune regulation by pneumococcus
肺炎球菌的免疫调节
基本信息
- 批准号:9317155
- 负责人:
- 金额:$ 23.25万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-07-07 至 2019-06-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAdherenceAmericanAutolysisBacteriaBacterial InfectionsBindingBronchus-Associated Lymphoid TissueCell physiologyCellsCenters for Disease Control and Prevention (U.S.)ClinicalContractsCytoplasmic GranulesDataDiseaseEffector CellEngineeringEscherichia coliFractionationFunding MechanismsGram-Positive BacteriaHospitalizationHost DefenseHumanImmuneImmune EvasionImmunological ModelsIndividualInfectionLaboratoriesLeadLocationLungMechanicsMembraneMemoryModelingMusNaturePeptide HydrolasesPneumococcal InfectionsPneumococcal PneumoniaPolysaccharidesPositioning AttributePredispositionProductionPropertyProteinsRegulationSamplingSeriesSerotypingSiteStreptococcus pneumoniaeStreptococcus pneumoniae plY proteinT cell differentiationT cell regulationT-Cell ActivationT-LymphocyteTestingTherapeuticTissuesVirulence FactorsWorld Health Organizationalanine aminopeptidasecapsulecombatcytokinedesignexperimental studyextracellulargenetic regulatory proteinimmune functionimmunoregulationinnovationinsightnovelpneumococcal surface protein Aresponse
项目摘要
At the global level, the World Health Organization (WHO) estimates there are ~14 million cases of
serious pneumococcal disease and more than 1.6 million people die each year from invasive pneumococcal
disease (IPD). Streptococcus pneumoniae has a number of virulence factors that contribute to its ability to
cause disease including polysaccharide capsule, pneumolysin and pneumococcal surface proteins A-C. We
have recently identified a novel immunoregulatory property of Spn. Our data show exposure of murine effector
cells to a soluble fraction generated from mechanically disrupted Spn results in effective inhibition of cytokine
production and granule release. The inhibition we observe is a highly novel and unexpected property of
pneumococcus. Importantly, this effect is not restricted to a single strain. We have tested an array of clinical
and laboratory isolates finding that all could inhibit T effector cell function.
In characterizing the inhibitory factor, we found it to be heat labile and protease sensitive. Through a
series of fractionation and sequencing approaches, candidate molecules were identified. Two candidates were
cloned, engineered to express a His tag, and expressed in E. coli allowing for efficient isolation and further
testing. Our data show that one of the candidates could reproduce the T cell inhibitory effect observed with
disrupted Spn and in addition, function was found to be independent of the known enzymatic activity of the
protein.
The ability of Spn to actively regulate function in effector cells presents a new mechanism for immune
regulation by this clinically important bacterium. The studies in this application are designed to understand
how the differentiation state of the T cell impact susceptibility to the negative regulatory protein. In addition, we
propose studies to elucidate the nature of the interaction of the regulatory protein with T cells. Finally, we will
determine the susceptibility of human T cells to the negative regulatory capabilities of Spn. These critical
questions will be addressed in the following aims. Aim 1 To determine how the differentiation state of a T cell
impacts its susceptibility to the immunoregulatory effects of Spn PepN. Aim 2 To determine whether PepN
interacts with the extracellular membrane or gains entry into the cell and the potential partners with which
PepN interacts. Aim 3 To determine how the presence of Spn components impacts function in human T cells.
在全球范围内,世界卫生组织(WHO)估计约有1400万例
项目成果
期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
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Martha Ann Alexander-Miller其他文献
Martha Ann Alexander-Miller的其他文献
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{{ truncateString('Martha Ann Alexander-Miller', 18)}}的其他基金
Development of vaccine approaches to elicit broadly protective influenza-specific immune responses in infants
开发疫苗方法以在婴儿中引发广泛保护性的流感特异性免疫反应
- 批准号:
10229523 - 财政年份:2020
- 资助金额:
$ 23.25万 - 项目类别:
Development of vaccine approaches to elicit broadly protective influenza-specific immune responses in infants
开发疫苗方法以在婴儿中引发广泛保护性的流感特异性免疫反应
- 批准号:
10456073 - 财政年份:2020
- 资助金额:
$ 23.25万 - 项目类别:
Vaccination strategies to overcome immune deficiencies in neonates
克服新生儿免疫缺陷的疫苗接种策略
- 批准号:
8840143 - 财政年份:2012
- 资助金额:
$ 23.25万 - 项目类别:
Vaccination strategies to overcome immune deficiencies in neonates
克服新生儿免疫缺陷的疫苗接种策略
- 批准号:
8477124 - 财政年份:2012
- 资助金额:
$ 23.25万 - 项目类别:
Vaccination strategies to overcome immune deficiencies in neonates
克服新生儿免疫缺陷的疫苗接种策略
- 批准号:
8668895 - 财政年份:2012
- 资助金额:
$ 23.25万 - 项目类别:
Vaccination strategies to overcome immune deficiencies in neonates
克服新生儿免疫缺陷的疫苗接种策略
- 批准号:
8319130 - 财政年份:2012
- 资助金额:
$ 23.25万 - 项目类别:
Cellular Immune Responses to Respiratory Infection
对呼吸道感染的细胞免疫反应
- 批准号:
7371984 - 财政年份:2004
- 资助金额:
$ 23.25万 - 项目类别:
Cellular Immune Responses to Respiratory Infection
对呼吸道感染的细胞免疫反应
- 批准号:
6867421 - 财政年份:2004
- 资助金额:
$ 23.25万 - 项目类别:
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