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

描述（由申请人提供）：我们先前的研究表明SIV感染恒河猴口腔粘膜中先天免疫应答失调。我们假设，这种失调是，在某种程度上，与发病机制的上皮细胞出现在原发性急性感染，并导致改变的组成的微生物菌群，创造一个生理生态位的病原体物种入侵。我们将测试这一假设的先天免疫反应和屏障功能的变化进行比较分析，发生在舌头，口咽，和颊囊上皮，发生在原发性和慢性阶段SIV感染恒河猴。SIV感染过程中口腔微生物组的变化将被表征为与上皮层中抗菌因子表达变化的关系，以及它们在口腔中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建立非人类灵长类动物的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测定。这些结果将增加我们对宿主上皮细胞中有助于居民口腔微生物菌群向患病状态口腔微生物菌群转变的分子机制的理解，并为未来的治疗进展提供潜在的生物标志物靶点，重点是预防或治疗HIV感染患者的机会性继发感染 公共卫生相关性：我们正在分析由猴免疫缺陷病毒（SIV）感染引起的宿主免疫应答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常驻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.