Defense of oral epithelial cells from candida by hBDs

由于艾滋病在欠发达世界的流行，在对高效抗逆转录病毒疗法(HAART)产生耐药性和滥用抗生素的情况下，没有高效抗逆转录病毒疗法(HAART)，口腔念珠菌感染正在重新出现。最近的发现指出，粘膜上皮细胞是抗菌和抗真菌药物的来源，属于一种称为人β-防御素(HBDS)的小阳离子多肽家族。我们最近发现了一种新的策略，通过这种策略，口腔中普遍存在的一种生物--核盘藻通过诱导hBD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细胞的趋化剂，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/或控制白念珠菌复制方面的重要性 获得性免疫细胞被招募到局部站点。这项提议旨在检验源于口腔上皮细胞可以被刺激产生β-防御素的假设，该β-防御素可以保护宿主免受口腔粘膜屏障处真菌的挑战。 由于hBDS在保护口腔粘膜上皮免受真菌生物膜生长方面的作用， 当细胞面对有益的和机会主义的有机体时，它们被调控的机制，其他HOEC衍生抗菌肽的存在，或者HBD的表达是否由于HIV而改变在HOEC中从未被系统地研究过，我们提供以下目标：(1)确定hBDS在HIV携带者和HIV+者的人口腔上皮细胞(HOECs)中核霉毒素激活后对抗白色念珠菌的重要性，(2)确定HOEC对白念珠菌挑战的细胞因子表达和利用Toll样受体和细胞内信号通路的反应。。 鉴于抗生素和抗真菌药物在治疗口腔疾病中的频繁辅助使用，以及微生物耐药性的威胁，研究新型真核多肽，如β-防御素，具有非常重要的意义，并提供了未来临床应用的潜力。这一新的研究方向被认为对引导未来的研究具有极其重要的意义，这些研究具有潜在的口腔疾病、治疗用途和技术开发的应用。

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.