Innate immunity and alteration of oral microbiome in SIV infected rhesus macaque

描述（由申请人提供）：我们之前的研究显示SIV感染的恒河猴口腔黏膜先天免疫反应失调。我们假设，这种失调在一定程度上与原发性急性感染中出现的上皮发病机制有关，并导致微生物群组成的变化，从而为致病物种的入侵创造生理生态位。我们将通过比较分析恒河猴原发性和慢性SIV感染期间舌头、口咽部和颊袋上皮内的先天免疫反应和屏障功能的变化来验证这一假设。在SIV感染过程中，口腔微生物组的改变将被表征为与上皮层抗菌因子表达的变化有关，以及它们在口腔机会性继发性感染发展中的潜在作用。拟议研究的数据还将用于建立非人类灵长类动物的类人猿口腔微生物组数据库（SOMD），并开发类人猿口腔微生物鉴定微阵列（SOMIM），以便在未来的研究中快速评估恒河猴的口腔微生物谱，涵盖各种口腔感染或疾病。该项目将在高度控制的实验环境中协调全面的细胞和分子分析。这些结果将增加我们对宿主上皮中导致常驻口腔微生物群向病变状态转变的分子机制的理解，并为未来治疗进展提供潜在的生物标志物靶标，重点是预防或治疗HIV感染患者的机会性继发性感染

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.