Defining the State of CD8+ and CD4+ T cells and the Effect of Antibiotic Treatment on Chronic States of Coccidioidomycosis Disease
定义 CD8 和 CD4 T 细胞的状态以及抗生素治疗对球孢子菌病慢性状态的影响
基本信息
- 批准号:10316113
- 负责人:
- 金额:$ 3.85万
- 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:2021-08-31 至 2023-08-30
- 项目状态:已结题
- 来源:
- 关键词:16S ribosomal RNA sequencingAIDS/HIV problemAcute DiseaseAerosolsAffectAntibiotic ResistanceAntibiotic TherapyAntibioticsAntifungal AgentsAsthmaBacteriaBacterial PneumoniaBronchoalveolar LavageCD4 Positive T LymphocytesCD8-Positive T-LymphocytesCD8B1 geneCancer EtiologyCell Differentiation processCellsCenters for Disease Control and Prevention (U.S.)Central AmericaChronicChronic DiseaseClinicalClostridium difficileCoccidioidesCoccidioides immitisCoccidioides posadasiiCoccidioidomycosisCommunicationCommunitiesCryptococcusDevelopmentDiagnosisDiseaseDisease MarkerDisease OutcomeDisease ProgressionExhibitsFilipinoFirmicutesGerm-FreeGlobal WarmingGoalsImmuneImmune responseImmunityImmunologic TestsImmunosuppressionInfectionInfluenza A Virus, H1N1 SubtypeInhalationInvadedLeadLiquid substanceLungLung diseasesLung infectionsMediatingModelingMucous MembraneMusMycosesOutcomePathway interactionsPatientsPersonsPlayPopulationPredispositionRegulatory T-LymphocyteReproduction sporesRespiratory distressRoleSalmonellaShigella flexneriSoilSouth AmericaStreptococcus pneumoniaeSymptomsT-Cell ActivationT-LymphocyteTestingUnited StatesUp-Regulationaccurate diagnosisaerosolizedbacterial resistancechronic infectioncommunity acquired pneumoniadesert feverdiabeticeffector T cellexhaustexhaustionexperienceflufungushigh risklung microbiomelung microbiotamicrobiomemicrobiome alterationnovel therapeuticspathogenpathogenic funguspredictive markerpreventreceptorreceptor expressionresponse
项目摘要
PROJECT SUMMARY
Coccidioidomycosis, also known as Valley fever, is a fungal infection caused by inhalation of Coccidioides
immitis and Coccidioides posadasii upon soil disturbance and aerosolization of the pathogen spores.
Coccidioides is endemic to Southwest United States, Central America, and South America and is found in hot,
dry regions. It is considered an emerging disease as it is spreading into non-endemic regions and is expected
to double in endemic region this century due to global warming. Valley fever can be a fatal fungal infection that
is often misdiagnosed as community acquired pneumonia and treated with several rounds of antibiotics prior to
accurate diagnosis. This contributes to a growing problem of antibiotic resistance and may also alter immune
responses to Coccidioides. We know that antibiotic treatment significantly shifts the lung microbiota repertoire
to being less diverse, with an increase in resistant bacteria, but it is unknown how antibiotics affect the
interrelationship between the host lung microbiome, the invading fungal pathogen, and the immune response.
The factors contributing to the development of Valley fever as either an acute or chronic disease are unknown.
Chronic infections often elicit CD4+ and CD8+ T cell exhaustion, characterized by an upregulation of inhibitory
pathways and a decrease in effector function. Suppression of T cell effector function by exhaustion could
promote chronic disease and serve as predictive markers of disease state. Thus, the goal of this proposal is to:
1) analyze the exhaustion state of CD4+ and CD8+ T cells in infected mice as a means of understanding the
host response; and 2) determine the impact antibiotic treatment has on disease outcome. I hypothesize that
CD4+ and CD8+ T cells develop an exhausted state, directly contributing to chronic fungal infection, and that
an altered microbiome through antibiotic treatment negatively impacts effective fungal clearance and
potentially enhances the rate of exhaustion.
项目总结
项目成果
期刊论文数量(0)
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Susana Tejeda-Garibay其他文献
Susana Tejeda-Garibay的其他文献
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{{ truncateString('Susana Tejeda-Garibay', 18)}}的其他基金
Defining the State of CD8+ and CD4+ T cells and the Effect of Antibiotic Treatment on Chronic States of Coccidioidomycosis Disease
定义 CD8 和 CD4 T 细胞的状态以及抗生素治疗对球孢子菌病慢性状态的影响
- 批准号:
10915081 - 财政年份:2021
- 资助金额:
$ 3.85万 - 项目类别:














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