Defense of oral epithelial cells from candida by hBDs

hBD 保护口腔上皮细胞免受念珠菌侵害

• 批准号: 7075771
• 负责人: AARON WEINBERG
• 金额: $ 27.04万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-15 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7075771
• 关键词: Candida albicans; Fusobacterium nucleatum; HIV infections; bacteria infection mechanism; biological signal transduction; cytokine; defensins; disease /disorder model; enzyme linked immunosorbent assay; gene expression; genetically modified animals; human subject; human tissue; laboratory mouse; messenger RNA; microarray technology; oral mucosa; toll like receptor

Oral candidal infections are re-emerging owing to the prevalence of AIDS in the under-developed world, where highly active antiretroviral therapy (HAART) is not available, in cases where resistance to HAART develops and in misuse of antibiotics. Recent findings point to mucosal epithelial cells as the sources of antibacterial and antifungal agents, belonging to a family of small, cationic peptides called human beta-defensins (hBDs). We recently discovered a novel strategy by which F. nucleatum, a ubiquitous organism of the oral cavity, protects human oral epithelial cells (HOECs) by inducing hBDs. Since they can kill the fungal pathogen Candida albicans, act as chemoattractants towards dendritic cells (DCs), monocytes and T cells and can induce maturation of DCs and monocytes, one can surmise the importance of these agents in preventing fungal infection at mucosal surfaces, and/or controlling C. albicans replication until acquired immune cells are recruited to the local site. This proposal intends to test hypotheses emanating from the postulate that oral epithelial cells can be stimulated to produce beta-defensins that protect the host from fungal challenges at the oral mucosal barrier. Since the role of hBDs in protecting the oral mucosal epithelium from fungal biofilm growth, the mechanisms by which they are regulated when cells are confronted by a beneficial versus opportunistic organism, the presence of other HOEC derived antimicrobial peptides, or whether hBD expression is altered in HOECs as a result of HIV, have never been systematically studied, we offer the following objectives: (1) to determine the importance of hBDs against C. albicans following F. nucleatum activation in human oral epithelial cells (HOECs) from HIV- and HIV+ individuals and (2) to define HOEC responses to C. albicans challenge as regards cytokine expression and utilization of toll-like receptors and intracellular signaling pathways. . In light of the frequent adjunctive use of antibiotics and antimycotics in treating oral diseases, with the threat of microbial resistance, investigations into novel eukaryotic peptides, such as beta-defensins, are highly significant and offer the potential for future clinical promise. This novel research direction is viewed as extremely significant in leading to future studies that have potential application to oral disorders, therapuetic use, and technology development.

由于艾滋病在不发达国家的流行，口腔念珠菌感染正在重新出现，这些国家没有高效抗逆转录病毒疗法（HAART），在对HAART产生耐药性的情况下以及滥用抗生素。最近的研究结果表明，粘膜上皮细胞是抗菌和抗真菌药物的来源，属于一个小的，阳离子肽家族，称为人β -防御素（hBDs）。我们最近发现了一种新的策略，即在口腔中普遍存在的具核梭菌通过诱导hBDs来保护人类口腔上皮细胞（HOECs）。由于它们可以杀死真菌病原体白色念珠菌，作为树突状细胞（dc）、单核细胞和T细胞的化学引诱剂，并可以诱导树突状细胞和单核细胞的成熟，因此可以推测这些药物在预防粘膜表面真菌感染和/或控制白色念珠菌复制方面的重要性