Investigating the role of Staphylococcus aureus strain-level diversity on neutrophil recruitment and wound healing in a cutaneous leishmaniasis infection
研究皮肤利什曼病感染中金黄色葡萄球菌菌株水平多样性对中性粒细胞募集和伤口愈合的作用
基本信息
- 批准号:10313240
- 负责人:
- 金额:$ 4.6万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-07-01 至 2024-06-30
- 项目状态:已结题
- 来源:
- 关键词:AmputationAntibodiesAutomobile DrivingBacteriaBiological MarkersBiopsyCellsChronicClassificationClinicalCutaneousCutaneous LeishmaniasisDataDiseaseDown-RegulationEpithelialEpithelial CellsFailureGene ActivationGene ExpressionGenesGenomeHumanImpaired healingImpaired wound healingIn VitroInfectionInflammationInflammatoryInflammatory ResponseInterleukin-8LeishmaniaLeishmania majorLeishmaniasisLesionMeasuresMediatingMessenger RNAMetadataMicrobeMigration AssayModelingMusNeutrophil InfiltrationOsteomyelitisOutcomeParasite ControlParasitesParasitic infectionPathologicPathologyPatient-Focused OutcomesPatientsPhenotypePhylogenetic AnalysisProcessProteinsPrunella vulgarisQuality of lifeReporterResearchResolutionRoleSepsisSeveritiesSiteSkinSkin TissueSkin injurySkin wound healingSoft Tissue InfectionsStaphylococcus aureusStaphylococcus aureus infectionTestingTimeTissuesTumor-infiltrating immune cellsVirulenceWorkWound InfectionWound modelschronic woundcomparative genomicscytokinediabetic ulcerdifferential expressiongenome sequencinghealingimmunopathologyin vivoinsightkeratinocytemicrobialmicrobiotamigrationmortalitymouse modelneutrophilnew therapeutic targetnovelpathogenresponseskin lesionskin microbiomeskin microbiotatranscriptome sequencingwhole genomewoundwound healing
项目摘要
PROJECT SUMMARY
Cutaneous leishmaniasis is a parasitic infection that causes a variable spectrum of disease ranging from
single, self-healing lesions to disfiguring chronic lesions that do not heal despite treatment. While the factors
driving lesion chronicity are not clear, it is evident that many of the most severe forms of the disease are caused
by uncontrolled inflammation rather than high parasite burden. In mice, chronic leishmaniasis lesions are
characterized by increased neutrophil accumulation, persistent activation of inflammatory cytokines, and
increased infiltration of immune cells to the lesion site, all of which exacerbate tissue damage and delay healing.
Our lab has previously shown that colonizing microbes on the skin contribute to immunopathology in murine
models, however the role of the skin microbiota in regulating lesion healing is not known. We have found that
the most common bacteria colonizing human cutaneous leishmania lesions is Staphylococcus aureus (S.
aureus) which delays wound healing in a strain-specific manner across many different pathologies and is a potent
neutrophil recruiter. We have also been able to show that S. aureus clinical isolates cultured from human
cutaneous leishmaniasis lesions induce secretion of different amounts of neutrophil chemotactic factors such as
interleukin-8 (IL-8) by epithelial cells in a wound setting. Therefore, the central hypothesis of my proposal is that
S. aureus delays cutaneous leishmaniasis lesion healing through strain-variable neutrophil recruitment and
accumulation. In Aim 1, I will determine the strain-specific effect of S. aureus-mediated neutrophil recruitment
on wound healing and immunopathology in both a wounding model and in a cutaneous leishmaniasis model
using LysM-EGFP mice. In Aim 2, I will identify differences S. aureus neutrophil recruitment and persistence
genes across clinical isolates using whole genome sequencing and comparative genomics and associate this
data with clinical outcomes and RNA sequencing gene expression from human cutaneous leishmaniasis lesions.
These findings will collectively drive understanding of the strain-specific effects of S. aureus infection and
neutrophil recruitment on wound healing, uncover biomarkers that can be used to predict patient outcome, and
identify novel therapeutic targets in the treatment of cutaneous leishmaniasis.
项目总结
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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Victoria Lovins其他文献
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{{ truncateString('Victoria Lovins', 18)}}的其他基金
Investigating the role of Staphylococcus aureus strain-level diversity on neutrophil recruitment and wound healing in a cutaneous leishmaniasis infection
研究皮肤利什曼病感染中金黄色葡萄球菌菌株水平多样性对中性粒细胞募集和伤口愈合的作用
- 批准号:
10454140 - 财政年份:2021
- 资助金额:
$ 4.6万 - 项目类别:
Investigating the role of Staphylococcus aureus strain-level diversity on neutrophil recruitment and wound healing in a cutaneous leishmaniasis infection
研究皮肤利什曼病感染中金黄色葡萄球菌菌株水平多样性对中性粒细胞募集和伤口愈合的作用
- 批准号:
10653953 - 财政年份:2021
- 资助金额:
$ 4.6万 - 项目类别:
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