Innate immunity and alteration of the oral microbiome in SIV infected rhesus maca

描述(申请人提供)：我们之前的研究表明，SIV感染的恒河猴口腔粘膜中存在先天免疫反应的失调。我们推测，这种失调在一定程度上与原发急性感染时出现的上皮细胞的发病机制有关，并导致微生物区系组成的变化，从而为病原物种入侵创造了一个生理生态位。我们将通过比较分析恒河猴在感染SIV原发阶段和慢性阶段时舌头、口咽和面颊囊上皮内发生的先天免疫反应和屏障功能的变化来检验这一假设。SIV感染过程中口腔微生物组的变化将被描述为与上皮层抗菌因子表达变化的关系，以及它们在口腔机会性继发感染发展中的潜在作用。拟议研究的数据还将用于启动为非人类灵长类建立猿猴口腔微生物组数据库(SOMD)，并开发猿猴口腔微生物鉴定微阵列(SOMIM)，以在未来涵盖各种口腔感染或疾病的研究中快速评估恒河猴的口腔微生物谱。该项目将在高度受控的实验环境中协调全面的细胞和分子分析。这一结果将增加我们对宿主上皮细胞分子机制的理解，这些分子机制有助于口腔常驻菌群向患病状态口腔菌群的转变，并为未来专注于预防或治疗hiv感染患者机会性继发感染的治疗进展提供潜在的生物标志物靶标。 公共卫生相关性：SIV感染猕猴的先天免疫和口腔微生物群的变化我们正在分析SIV感染导致的宿主免疫反应和口腔上皮层保护功能的变化。我们将确定这些变化是否出现在感染的早期、初级阶段，以及这些变化如何影响口腔中驻留的细菌微生物群的组成，并与继发性机会性感染的发生相关。

DESCRIPTION (provided by applicant): Our previous studies have shown a dysregulation of innate immune responses in the oral mucosa of SIV infected rhesus macaques. We hypothesize that this dysregulation is, in part, associated with pathogenesis of the epithelium that emerges in primary acute infection, and leads to changes to the composition of the microflora that create a physiological niche for pathogenic species to invade. We will test this hypothesis by comparative analysis of the changes in innate immune response and barrier functions occurring within the tongue, oropharynx, and cheek pouch epithelium that occur during primary and chronic stage SIV infection in rhesus macaques. Alterations in the oral microbiome during the course of SIV infection will be characterized as to relationship to changes in expression of antimicrobial factors in the epithelial layer, and their potential role in the development of opportunistic secondary infections in the oral cavity. Data from the proposed studies will also be utilized to initiate the establishment of a Simian Oral Microbiome Database (SOMD) for non-human primates, and to develop a Simian Oral Microbe Identification Microarray (SOMIM) to rapidly assess the oral microbial profiles of rhesus monkeys in future studies covering a variety of oral infections or conditions. The project will coordinate comprehensive cellular and molecular assays in a highly controlled experimental environment. The results will increase our understanding of the molecular mechanisms in the host epithelium that contribute to the shift of resident oral microflora to diseased state oral microflora, and provide potential biomarker targets for future therapeutic advances that focus on preventing or curing opportunistic secondary infections in HIV infected patients PUBLIC HEALTH RELEVANCE: ,Innate immunity and alteration of the oral microbiome in SIV infected rhesus macaques We are analyzing changes in host immune responses and protective functions of the oral epithelial layer that result from simian immunodeficiency virus (SIV) infection. We will determine if these changes emerge in the early, primary stage of infection, and how the changes impact the composition of the resident bacterial microflora in the oral cavity and correlate with the onset of secondary opportunistic infections.