Proj. 4-The Genetic Variation of Innate Immune Genes w/Oral Manifestations of HIV

自2001年艾滋病毒/艾滋病流行病首次出现以来， 80年代。最常见的口腔并发症是念珠菌病， CD 4 +T细胞。口腔念珠菌感染是免疫功能障碍的标志性指标。增加的 机会性感染的发生率与免疫抑制有关， CD 4 + T细胞的数量和功能活性。口腔并发症的频率和类型发生了变化 从80年代的最初描述开始。随着HAART疗法的开始，口服 表现形式发生了变化。人乳头瘤病毒相关疣和重型阿弗他溃疡性口腔炎的发病率 增加，而口腔念珠菌感染和口腔毛状白斑有所下降。此外，并非所有 患者发展这些病理。疾病表现和伴随反应的变化 治疗可能与先天免疫基因的遗传易感性和上皮屏障的变化有关 功能先天免疫越来越被认为在宿主防御中起着关键作用， 传染病，包括艾滋病毒。防御素肽具有抗微生物性质，并且是主要的抗微生物肽。 上皮粘膜屏障的保护成分。防御素基因的遗传变异 SNPs和CNVs的突变与疾病易感性有关。Toll样受体（TLR）， 包括人口腔上皮细胞在内的宿主细胞上的进化保守受体家族，识别 特定的微生物结构，导致炎症介质的上调和 炎症细胞微生物与宿主组织的多重相互作用及分泌的抗菌分子 例如β-防御素参与维持健康人的体内平衡环境 然而，关于TLR在这一过程中的作用或HIV疾病对这些作用的影响，人们知之甚少。 流程. TLR家族的多态性和常见的衔接子TIRAP/Mal与 许多人类传染病和自身免疫性疾病。我们假设宿主TLRs的变异及其 信号成分通过改变HIV疾病中的口腔感染， 宿主/微生物在粘膜表面的相互作用。我们将破译基因变异之间的关系， 防御素基因簇和Toll样受体TLR 1和TLR 2均与HIV/AIDS的口腔表现有关。我们 将定义和关联特定的复杂单倍型与口腔病变的频率和发生， 艾滋病毒感染者。我们假设HIV的易感性、预后和结果与 防御素基因簇的遗传变异。这种相同的变化也可以与 HIV感染后口腔并发症的发展

Oral manifestations of HIV have been documented since the initial presentation of the HIV/AIDS epidemic of the 80's. The most common oral complication was candidiasis, and was associated with a reduction in CD4+T cells. Oral candidal infection was a hallmark indicator of immune dysfunction. The increased incidence of opportunistic infections was related to immune suppression as evidenced by a reduction in number and functional activity of CD4 + T cells. The frequency and type of oral complication has changed since the initial description of the 80s. With the initiation of HAART therapies the constellation of oral manifestations has changed. The incidence of HPV associated warts and severe aphthous ulcer stomatitis has increased, whereas oral candidal infection and oral hairy leukoplakia has declined. In addition, not all patients develop these pathologies. The variation in disease presentation and concomitant response to therapy may be related to genetic predisposition of innate immune genes and variation in epithelial barrier function. Innate immunity is increasingly being recognized as playing a critical role in host defense against infectious diseases, including HIV. The defensin peptides have antimicrobial properties and are major protective components of the epithelial mucosal barrier. Genetic variation of the defensin genes in the form of SNPs and CNVs has been shown to be associated with disease susceptibility. Toll-like receptors (TLRs), a family of evolutionary conserved receptors on host cells including human oral epithelial cells, recognize specific microbial structures, leading to the up-regulation of inflammatory mediators and recruitment of inflammatory cells. Multiple interactions of microbes and host tissues and secreted antimicrobial molecules such as beta-defensins are involved in the maintenance of the homeostatic environment of the healthy mouth, however, little is known about the role of TLRs in this process or the impact of HIV disease on these processes. Polymorphisms in the TLR family and the common adaptor Tirap/Mal have been associated with many human infectious and autoimmune diseases. We hypothesize that host variation in TLRs and their signaling components contribute to the variability in oral infections seen in HIV disease by altering host/microbe interactions at the mucosal surface. We will decipher the relationship of genetic variations in both the defensin gene cluster and toll-like receptors TLR1 and 2 with oral manifestations of HIV/AIDS. We will define and correlate specific complex haplotypes with the frequency and occurrence of oral lesions in the HIV population. We hypothesize that susceptibility, prognosis, and outcome of HIV are associated with genetic variations in the defensin gene cluster. This same variation also may be associated with the development of oral complications following HIV infection