Role of extraceullar vesicles in directing immunometabolic homeostasis after burn injury
细胞外囊泡在烧伤后指导免疫代谢稳态中的作用
基本信息
- 批准号:10337838
- 负责人:
- 金额:$ 1.74万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-12-15 至 2022-11-30
- 项目状态:已结题
- 来源:
- 关键词:AmericanAnimal ModelAnti-Inflammatory AgentsAntigen-Antibody ComplexAutomobile DrivingBacteremiaBacterial InfectionsBindingBiological Response ModifiersBurn CentersBurn injuryCellsCessation of lifeClinicalCytokine SignalingDataDevelopmentDevelopment PlansEndothelial CellsEnsureEnzymesEpithelialEpithelial CellsExperimental DesignsFRAP1 geneGlycolysisGoalsGraft RejectionGrantHomeostasisHumanImmuneImmune System DiseasesImmune responseImmune signalingImmunomodulatorsImmunosuppressionInfectionInflammationInflammatoryInflammatory ResponseInhalationInjuryInterleukin-10InvestigationLeadLeukocytesLungMediatingMetabolicMicroRNAsMolecularMorbidity - disease rateMusNational Institute of General Medical SciencesOpportunistic InfectionsOutcomePPAR gammaParentsPathologyPathway interactionsPatient-Focused OutcomesPatientsPatternPattern recognition receptorPhasePhenotypePlasmaPlayPneumoniaPopulationPre-Clinical ModelPredispositionReceptor SignalingResearchResearch TrainingRoleSamplingSepsisSignal TransductionStimulusTestingTissuesToll-like receptorsTrainingTraumaUnited StatesVesiclearginaseburn modelcareercareer developmentcytokineexperienceextracellularextracellular vesicleshigh riskimmune activationimmune functionimprovedindexinginnate immune functionlung injurymacrophagemicrovesiclesmortalityneutrophilnovelparent grantpre-doctoralpreclinical studyprognostic valuereceptor expressionrecruitrepositoryresponsesevere burnssystemic inflammatory response
项目摘要
ABSTRACT
The research and training plan put forth in this Diversity Supplement will build upon key findings generated under
the parent application by the pre-doctoral candidate (Micah LaTrell Willis). This Research Plan and the Training
Plan submitted will provide Mr. Willis with opportunities to not only build an intellectual and technical toolbox to
propel him towards the next phase of his trainee/development but provide him the career development
opportunities to ensure he obtains his short and long-term career goals. Thus, support from this this Diversity
Supplement will empower Mr. Willis to own and drive his research, training, and career development plans.
Severe burn injury is one of the most devastating forms of trauma, with mortality rates reaching up to 12% even
in specialized burn centers. Combined inhalation injury further increases this mortality rate. The primary cause
of mortality are opportunistic infections which occur days to weeks after the injury, often resulting in lethal
pneumonias and/or sepsis from bacteremia. Burn-induced immune dysfunction underlies this prolonged
susceptibility to infection. It is known that response to bacterial infections is induced and regulated by Toll-like
Receptor (TLR) and associated MyD88 signaling, causing release of key inflammatory cytokines. With our parent
NIGMS grant “Damage-Induced Activation of the TLR/mTOR/PPARg Axis Regulates the Immune Response
After Burn and Inhalation Injury” (R01GM131124), we are currently investigating in human and pre-clinical
studies that immune dysfunction after burn and inhalation injury involves aberrant MyD88-mediated TLR
signaling by damage associated molecular pattern molecules (DAMPs) released after injury. This results in
aberrant cytokine signaling, with macrophages, neutrophils and endothelial cells (EC) playing key roles.
Extracellular vesicles have emerged as novel mediators of immune dysfunction across several immune
pathologies. Microvesicles (MVs) are a class of extracellular vesicles that carry DAMPs, cytokines, and miRNAs,
to regulate functions of recipient cells. We have found that MVs are a key reservoir for DAMPs, cytokines, and
potent immune complexes after burn injury in humans and mice. Given our findings, and the key role of MVs in
multiple immune conditions, we hypothesize that MVs drive the immune dysfunction associated with poor clinical
outcomes in severe burn injury. These findings are highly synergistic with the Specific Aims of the parent
grant. Using same patient and mouse tissue (utilizing our established pre-clinical model of burn and inhalation
injury, and repository of human burn patient samples) derived during the parent grant’s experimental plan, we
aim to further characterize the payload (Supplement Aim 1) and immune function (Supplement Aim 2) of MVs
isolated from plasma after injury. This will allow us to incorporate MVs into the Immune Suppression Index (ISI)
developed in the parent grant to identify burn patients at low and high risk for subsequent bacterial infection to
improve prognostic value
摘要
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Bruce A Cairns其他文献
Bruce A Cairns的其他文献
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{{ truncateString('Bruce A Cairns', 18)}}的其他基金
Multi-modal rescue of pulmonary NRF2-insufficiency after burn and burn + inhalation injury to regulate innate immune dysfunction
烧伤及烧伤吸入性损伤后肺NRF2不足的多模式抢救调节先天免疫功能障碍
- 批准号:
10435748 - 财政年份:2022
- 资助金额:
$ 1.74万 - 项目类别:
Multi-modal rescue of pulmonary NRF2-insufficiency after burn and burn + inhalation injury to regulate innate immune dysfunction
烧伤及烧伤吸入性损伤后肺NRF2不足的多模式抢救调节先天免疫功能障碍
- 批准号:
10732822 - 财政年份:2022
- 资助金额:
$ 1.74万 - 项目类别:
Multi-modal rescue of pulmonary NRF2-insufficiency after burn and burn + inhalation injury to regulate innate immune dysfunction
烧伤及烧伤吸入性损伤后肺NRF2不足的多模式抢救调节先天免疫功能障碍
- 批准号:
10651857 - 财政年份:2022
- 资助金额:
$ 1.74万 - 项目类别:
Damage-Induced Activation of the TLR/mTOR/PPARg Axis Regulates the Immune Response After Burn and Inhalation Injury
损伤诱导的 TLR/mTOR/PPARg 轴激活调节烧伤和吸入性损伤后的免疫反应
- 批准号:
10300052 - 财政年份:2018
- 资助金额:
$ 1.74万 - 项目类别:
Damage-Induced Activation of the TLR/mTOR/PPARg Axis Regulates the Immune Response After Burn and Inhalation Injury
损伤诱导的 TLR/mTOR/PPARg 轴激活调节烧伤和吸入性损伤后的免疫反应
- 批准号:
10062997 - 财政年份:2018
- 资助金额:
$ 1.74万 - 项目类别:
Damage-Induced Activation of the TLR/mTOR/PPARg Axis Regulates the Immune Response After Burn and Inhalation Injury
损伤诱导的 TLR/mTOR/PPARg 轴激活调节烧伤和吸入性损伤后的免疫反应
- 批准号:
10531808 - 财政年份:2018
- 资助金额:
$ 1.74万 - 项目类别:
Cellular mechanism of immune dysfunction following burn injury
烧伤后免疫功能障碍的细胞机制
- 批准号:
8445370 - 财政年份:2009
- 资助金额:
$ 1.74万 - 项目类别:
Cellular mechanism of immune dysfunction following burn injury
烧伤后免疫功能障碍的细胞机制
- 批准号:
7799750 - 财政年份:2009
- 资助金额:
$ 1.74万 - 项目类别:
Cellular mechanism of immune dysfunction following burn injury
烧伤后免疫功能障碍的细胞机制
- 批准号:
8244359 - 财政年份:2009
- 资助金额:
$ 1.74万 - 项目类别:
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