ORAL EPITHELIAL CELL CYTOKINES--CANDIDA & PMN ACTIVATION
口腔上皮细胞细胞因子--念珠菌
基本信息
- 批准号:6286620
- 负责人:
- 金额:$ 21.74万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2000
- 资助国家:美国
- 起止时间:2000-09-29 至 2003-07-31
- 项目状态:已结题
- 来源:
- 关键词:Candida albicans candidiasis cellular immunity clinical research colony stimulating factor cytokine gingiva host organism interaction human subject interleukin 1 leukocyte activation /transformation mixed tissue /cell culture mucosal immunity neutrophil oral mucosa pathologic process phagocytosis statistics /biometry
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
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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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:
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 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 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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