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
球孢子菌病,也称为谷热,是一种因吸入球孢子菌素而引起的真菌感染
球孢子虫和球孢子虫对土壤扰动和病原菌孢子气雾化的影响。
球孢子虫是美国西南部、中美洲和南美洲的特有种,在炎热的
干旱地区。它被认为是一种新出现的疾病,因为它正在向非流行地区扩散,预计
由于全球变暖,本世纪地方病流行地区的人口将增加一倍。山谷热可能是一种致命的真菌感染,
经常被误诊为社区获得性肺炎,并在治疗前接受了几轮抗生素治疗
准确的诊断。这导致了日益严重的抗生素耐药性问题,并可能改变免疫系统
对球孢子虫的反应。我们知道抗生素治疗显著改变了肺部微生物区系。
变得不那么多样化,耐药细菌增加,但尚不清楚抗生素是如何影响
宿主肺微生物群、入侵真菌病原体和免疫反应之间的相互关系。
谷热发展为一种急性或慢性疾病的因素尚不清楚。
慢性感染通常导致CD4+和CD8+T细胞耗尽,其特征是抑制性上调
途径和效应器功能的下降。衰竭对T细胞效应器功能的抑制可能
促进慢性疾病,并作为疾病状态的预测标志。因此,这项提议的目标是:
1)分析感染小鼠外周血中CD4+和CD8+T细胞的耗竭状态,以了解
宿主反应;以及2)确定抗生素治疗对疾病结局的影响。我假设
CD4+和CD8+T细胞进入衰竭状态,直接导致慢性真菌感染,
通过抗生素治疗而改变的微生物群对有效的真菌清除和
可能会增加精疲力竭的速度。
项目成果
期刊论文数量(0)
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Susana Tejeda-Garibay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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