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: 7095126
• 负责人: AARON WEINBERG
• 金额: $ 26.4万
• 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/7095126
• 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.

由于在不发达的世界中艾滋病的流行，口服候选感染正在重新出现，在这种情况下，在高度活跃的抗逆转录病毒疗法（HAART）的情况下，在HAART的抵抗力发展并滥用抗生素的情况下。最近的发现指出，粘膜上皮细胞是抗菌和抗真菌剂的来源，属于一个小的阳离子肽家族，称为人β-防御素（HBD）。我们最近发现了一种新型策略，该策略是通过诱导HBD来保护人类口腔上皮细胞（HOEC）的一种无处不在的生物F. nucleatum。由于它们可以杀死真菌病原体念珠菌白色念珠菌，因此充当对树突状细胞（DC），单核细胞和T细胞的化学吸引力，并且可以诱导DCS和单核细胞的成熟，因此可以刺激这些药物在防止粘膜表面上的真菌感染和/或控制C. C. albicans C. albicisans C. albicics c. albicics c. albiccics obcicass obcics obcicass opc. 获得的免疫细胞被招募到当地部位。该提案旨在测试可以刺激口腔上皮细胞产生的假设，以产生β-防御素，以保护宿主免受口腔粘膜屏障的真菌挑战。 由于HBD在保护口腔粘膜上皮免受真菌生物膜生长中的作用，因此 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 （HOEC）从HIV-和HIV+个体以及（2）定义对白色念珠菌的HOEC反应，挑战细胞因子的表达和收费类受体的利用和细胞内信号通路的利用。 。 鉴于抗生素和抗菌落药在治疗口腔疾病中的辅助使用，并具有微生物耐药性的威胁，对新型真核肽（例如β-防御素）的研究非常重要，并为未来的临床前景提供了潜力。这个新颖的研究方向在导致未来的研究中被视为极为重要，这些研究可能适用于口腔疾病，治疗方法和技术开发。