Moutsopoulos Niki M, Nares Salvador, Nikitakis Nikolaos, Rangel Zoila, Wen Jie, Munson Peter, Sauk John, Wahl Sharon M
Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda 20892, USA.
Am J Pathol. 2007 Aug;171(2):571-9. doi: 10.2353/ajpath.2007.061006. Epub 2007 Jul 9.
Tonsil epithelium has been implicated in human immunodeficiency virus (HIV) pathogenesis, but its role in oral transmission remains controversial. To study characteristics of this tissue, which may influence susceptibility or resistance to HIV, we performed microarray analysis of the tonsil epithelium. Our data revealed that genes related to immune functions such as antibody production and antigen processing were increasingly expressed in tonsil compared with the epithelium of another oropharyngeal site, the gingival epithelium. Importantly, tonsil epithelium highly expressed genes associated with HIV entrapment and/or transmission, including the HIV co-receptor CXCR4 and the potential HIV-binding molecules FcRgammaIII, complement receptor 2, and various complement components. Immunohistochemical staining confirmed the increased presence of CXCR4 in the tonsil epithelium compared with multiple oral epithelial sites, particularly in basal and parabasal layers. This increased expression of molecules involved in viral recognition, binding, and entry may favor virus-epithelium interactions in an environment with reduced innate antiviral mechanisms. Specifically, secretory leukocyte protease inhibitor, an innate molecule with anti-HIV activity, was minimal in the tonsil epithelium, in contrast to oral mucosa. Collectively, our data suggest that increased expression of molecules associated with HIV binding and entry coupled with decreased innate antiviral factors may render the tonsil a potential site for oral transmission.
扁桃体上皮细胞与人类免疫缺陷病毒(HIV)的发病机制有关,但其在口腔传播中的作用仍存在争议。为了研究该组织可能影响对HIV易感性或抵抗力的特征,我们对扁桃体上皮细胞进行了微阵列分析。我们的数据显示,与免疫功能相关的基因,如抗体产生和抗原加工,在扁桃体中的表达比另一个口咽部位——牙龈上皮细胞中的表达增加。重要的是,扁桃体上皮细胞高度表达与HIV捕获和/或传播相关的基因,包括HIV共受体CXCR4以及潜在的HIV结合分子FcRγIII、补体受体2和各种补体成分。免疫组织化学染色证实,与多个口腔上皮部位相比,CXCR4在扁桃体上皮细胞中的表达增加,特别是在基底层和副基底层。在先天抗病毒机制减弱的环境中,参与病毒识别、结合和进入的分子表达增加可能有利于病毒与上皮细胞的相互作用。具体而言,与口腔黏膜相比,具有抗HIV活性的先天分子分泌型白细胞蛋白酶抑制剂在扁桃体上皮细胞中的含量极少。总的来说,我们的数据表明,与HIV结合和进入相关的分子表达增加,同时先天抗病毒因子减少,可能使扁桃体成为口腔传播的潜在部位。