ORAL EPITHELIAL CELL CYTOKINES--CANDIDA & PMN ACTIVATION

口腔上皮细胞细胞因子--念珠菌

基本信息

项目摘要

DESCRIPTION: (abstract verbatim) Oropharyngeal candidiasis is particularly prevalent in patients who are immunocompromised by disease or immunosuppressive treatment. Interestingly, even in immunocompromised patients invasive oral candidiasis is rare and seems to be associated with additional risk factors such as extreme neutropenia. One strategy for improving resistance to opportunistic pathogens is to define host cellular responses during the invasion process and enhance those responses that are relevant to defense mechanisms. Compelling experimental evidence suggests that the primary effector cell responsible for Candida clearance is the neutrophil. Neutrophils accumulate rapidly at the site of infection in the oral cavity and participate in the local control of Candida growth and invasion, yet very little is known about the host signals responsible for regulating these events. Several cytokines provide signals for neutrophil activation of antifungal functions, including interleukin-1 beta (IL-1b) and granulocyte macrophage colony stimulating factor (GM-CSF). In cases of T-helper cell depletion or inactivation, such as HIV disease or Cyclosporin A treatment, PMN are most likely potentiated in their anti-fungal function by stimulating cytokines derived from non-immune cell. Epithelial cells are capable of synthesizing IL-1b and GM-CSF and maybe one of the few defenses remaining under CD+ T cell-deficient conditions. The central hypothesis of this project is that cytokines such as IL-1b and GM-CSF are released by oral epithelial cells upon interaction with Candida and act as local stimulators of neutrophil anti-fungal functions. Using a human oral epithelial cell Candida albicans coculture model system the applicants will first determine whether this microorganism can trigger secretion of these potent neutrophil activating cytokines by oral epithelial cells. Once this goal is accomplished, mechanisms eliciting Candida-mediated cytokine responses will be explored. Finally, they will perform functional assays for these epithelial cell-derived cytokines as they relate to neutrophil activation of Candida phagocytosis and killing, using isolated neutrophils from healthy, HIV+ and Cyclosporine A-treated individuals. Given the fact that most fungal infections take place in an immunocompromised host, neutrophil priming by non-immune cell derived cytokines may be of paramount importance, not just in the initiation of a protective inflammatory response, but also in the prevention of fungal invasion into the deeper connective tissues of the oral mucosa. The studies proposed herein will be crucial in identifying oral epithelial cell-derived cytokines with the potential to prime neutrophil antifungal function in vitro. Identification of such cytokines may have future therapeutic applications in the treatment of oral candidiasis in the severely immunocompromised host.
描述:(摘要逐字逐句)口咽念珠菌病尤甚

项目成果

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Anna I Dongari-Bagtzoglou其他文献

Anna I Dongari-Bagtzoglou的其他文献

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{{ truncateString('Anna I Dongari-Bagtzoglou', 18)}}的其他基金

Control of heterogeneous microbial communities using model-based multi-objective optimization
使用基于模型的多目标优化控制异质微生物群落
  • 批准号:
    10268262
  • 财政年份:
    2018
  • 资助金额:
    $ 21.74万
  • 项目类别:
Control of heterogeneous microbial communities using model-based multi-objective optimization
使用基于模型的多目标优化控制异质微生物群落
  • 批准号:
    10267334
  • 财政年份:
    2018
  • 资助金额:
    $ 21.74万
  • 项目类别:
Model of chemotherapy-induced mucositis
化疗引起的粘膜炎模型
  • 批准号:
    8871565
  • 财政年份:
    2014
  • 资助金额:
    $ 21.74万
  • 项目类别:
Model of chemotherapy-induced mucositis
化疗引起的粘膜炎模型
  • 批准号:
    8770223
  • 财政年份:
    2014
  • 资助金额:
    $ 21.74万
  • 项目类别:
Oral Epithelial Cells, Candida and PMN Activation
口腔上皮细胞、念珠菌和 PMN 激活
  • 批准号:
    7932529
  • 财政年份:
    2009
  • 资助金额:
    $ 21.74万
  • 项目类别:
ORAL INFECTION AND INFLAMMATION IN TRANSPLANT PATIENTS
移植患者的口腔感染和炎症
  • 批准号:
    7719123
  • 财政年份:
    2008
  • 资助金额:
    $ 21.74万
  • 项目类别:
ORAL CANDIDA
口腔念珠菌
  • 批准号:
    7719112
  • 财政年份:
    2008
  • 资助金额:
    $ 21.74万
  • 项目类别:
ORAL INFECTION AND INFLAMMATION IN TRANSPLANT PATIENTS
移植患者的口腔感染和炎症
  • 批准号:
    7607625
  • 财政年份:
    2007
  • 资助金额:
    $ 21.74万
  • 项目类别:
ORAL CANDIDA
口腔念珠菌
  • 批准号:
    7607610
  • 财政年份:
    2007
  • 资助金额:
    $ 21.74万
  • 项目类别:
ORAL INFECTION AND INFLAMMATION IN TRANSPLANT PATIENTS
移植患者的口腔感染和炎症
  • 批准号:
    7377365
  • 财政年份:
    2006
  • 资助金额:
    $ 21.74万
  • 项目类别:

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Candida and Candidiasis Conference 2023
2023 年念珠菌和念珠菌病会议
  • 批准号:
    10682982
  • 财政年份:
    2023
  • 资助金额:
    $ 21.74万
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Functional analysis of the signaling adaptor protein during oral candidiasis
口腔念珠菌病期间信号转接蛋白的功能分析
  • 批准号:
    23H03076
  • 财政年份:
    2023
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    $ 21.74万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Discovery of bacterial consortia to treat recurrent vulvovaginal candidiasis: a generalizable platform for phenotypic microbial community screening
发现治疗复发性外阴阴道念珠菌病的细菌群落:表型微生物群落筛查的通用平台
  • 批准号:
    10383360
  • 财政年份:
    2022
  • 资助金额:
    $ 21.74万
  • 项目类别:
Development of theranostics system for oral candidiasis
口腔念珠菌病治疗诊断系统的开发
  • 批准号:
    22K10128
  • 财政年份:
    2022
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    $ 21.74万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Host and Fungal Regulation of Type 17 Immunity to Oral Candidiasis
17 型口腔念珠菌病免疫的宿主和真菌调节
  • 批准号:
    10551422
  • 财政年份:
    2022
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    $ 21.74万
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The development of invasive candidiasis prevention based on interactions between gastrointestinal microbiota and Candida species
基于胃肠道微生物群和念珠菌物种之间相互作用的侵袭性念珠菌病预防的发展
  • 批准号:
    20K17477
  • 财政年份:
    2022
  • 资助金额:
    $ 21.74万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
Host and Fungal Regulation of Type 17 Immunity to Oral Candidiasis
17 型口腔念珠菌病免疫的宿主和真菌调控
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    10673918
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    2022
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Mechanisms of renal protection against disseminated candidiasis
抵抗播散性念珠菌病的肾脏保护机制
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    10376250
  • 财政年份:
    2021
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    $ 21.74万
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Role of environmental iron in Candida albicans cell wall remodeling and its effect on host-pathogen interaction during oropharyngeal candidiasis
环境铁在口咽念珠菌病期间白色念珠菌细胞壁重塑中的作用及其对宿主-病原体相互作用的影响
  • 批准号:
    10647656
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    2021
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(Mis)Managing Microbiomes: Experiences and Challenges with Chronic Vulvovaginal Candidiasis in Primary Health Care
(错误)管理微生物组:初级卫生保健中慢性外阴阴道念珠菌病的经验和挑战
  • 批准号:
    457221
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    2021
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  • 项目类别:
    Studentship Programs
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