Defense of oral epithelial cells from candida by hBDs

由于艾滋病在不发达世界的流行，口腔念珠菌感染正在重新出现，因为在不发达世界没有高效抗逆转录病毒疗法，在对高效抗逆转录病毒疗法产生抗药性的情况下，以及在滥用抗生素的情况下。最近的研究结果指出，粘膜上皮细胞作为抗细菌和抗真菌剂的来源，属于称为人β-防御素（hBD）的小阳离子肽家族。我们最近发现了一种新的策略，通过这种策略，F。具核质是口腔中普遍存在的生物体，通过诱导hBD来保护人口腔上皮细胞（HOEC）。由于它们可以杀死真菌病原体白色念珠菌（Candida albicans），作为针对树突状细胞（DCs）、单核细胞和T细胞的化学引诱剂，并且可以诱导DCs和单核细胞的成熟，因此可以证实这些试剂在预防粘膜表面的真菌感染和/或控制念珠菌中的重要性。白色念珠菌复制， 获得性免疫细胞被募集到局部位点。该提案旨在测试源自以下假设的假设：口腔上皮细胞可以被刺激以产生β-防御素，其保护宿主免受口腔粘膜屏障处的真菌挑战。 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， 当细胞面对有益微生物或机会微生物时，它们的调节机制，其它HOEC衍生的抗微生物肽的存在，或者hBD表达是否由于HIV而在HOEC中改变，这些从未被系统地研究过，我们提供了以下目的：（1）确定hBD抗C. albicans继F.在HIV-和HIV+个体的人口腔上皮细胞（HOEC）中的具核质激活和（2）确定HOEC对C.白念珠菌在细胞因子表达和Toll样受体的利用以及细胞内信号传导途径方面的挑战。. 鉴于抗生素和抗真菌药在治疗口腔疾病中的频繁连续使用，以及微生物耐药性的威胁，对新型真核生物肽如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。这一新的研究方向被认为是非常重要的，在导致未来的研究，有潜在的应用到口腔疾病，治疗使用和技术开发。

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.