INNATE MUCOSAL IMMUNITY IN SIVMAC-INFECTED MACAQUES

SIVMAC 感染的猕猴的先天粘膜免疫

• 批准号: 7716300
• 负责人: Ivona Vasile Pandrea
• 金额: $ 6.33万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-21 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7716300
• 关键词: Antibody Formation; Antiviral Agents; Biopsy; CXCL10 gene; CXCL9 gene; Computer Retrieval of Information on Scientific Projects Database; Data; Disease Progression; Funding; Gene Expression; Genes; Goals; Grant; HIV; Immune response; Infection; Institution; Interferon Type II; Interferons; Ligase; Location; Macaca; Macaca mulatta; Messenger RNA; Mucosal Immunity; Oral; Oral mucous membrane structure; Plasma; Proteins; Reaction Time; Research; Research Personnel; Resources; SIV; Simian Acquired Immunodeficiency Syndrome; Source; Time; United States National Institutes of Health; Viral Load result; Virus Diseases; chemokine; cytokine; day; lymph nodes; mRNA Expression; mucosal site; oligoadenylate; response; transmission process

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Mucosal transmission is the predominant mode of human immunodeficiency virus (HIV) infection worldwide, and the mucosal innate interferon response represents an important component of the earliest host response to the infection. Our goal here was to assess the changes in mRNA expression of innate mucosal genes after oral simian immunodeficiency virus (SIV) inoculation of rhesus macaques (Macaca mulatta) that were followed throughout their course of disease progression. The SIV plasma viral load was highest in the macaque that progressed rapidly to simian AIDS (99 days) and lowest in the macaque that progressed more slowly (700 days). The mRNA levels of six innate/effector genes in the oral mucosa indicated that slower disease progression was associated with increased expression of these genes. This distinction was most evident when comparing the slowest-progressing macaque to the intermediate and rapid progressors. Expression levels of alpha and gamma interferons, the antiviral interferon-stimulated gene product 2'-5' oligoadenylate synthetase (OAS), and the chemokines CXCL9 and CXCL10 in the slow progressor were elevated at each of the three oral mucosal biopsy time points examined (day 2 to 4, 14 to 21, and day 70 postinfection). In contrast, the more rapidly progressing macaques demonstrated elevated levels of these cytokine/chemokine mRNA at lymph nodes, coincident with decreased levels at the mucosal sites, and a decreased ability to elicit an effective anti-SIV antibody response. These data provide evidence that a robust mucosal innate/effector immune response is beneficial following lentiviral exposure; however, it is likely that the anatomical location and timing of the response need to be coordinated to permit an effective immune response able to delay progression to simian AIDS.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 粘液传播是人类免疫缺陷病毒（HIV）感染的主要方式，并且粘膜先天性干扰素应答代表了对感染的最早宿主应答的重要组成部分。我们的目标是评估先天性粘膜基因的mRNA表达的变化后，口服猴免疫缺陷病毒（SIV）接种恒河猴（猕猴），随后在整个病程的疾病进展。SIV血浆病毒载量在快速进展为类人猿艾滋病（99天）的猕猴中最高，在进展较慢（700天）的猕猴中最低。口腔粘膜中6个先天/效应基因的mRNA水平表明，疾病进展较慢与这些基因的表达增加有关。这种区别在将进展最慢的猕猴与中间和快速进展者进行比较时最为明显。α和γ干扰素、抗病毒干扰素刺激的基因产物2 '-5'寡腺苷酸合成酶（OAS）以及趋化因子CXCL 9和CXCL 10在慢进展者中的表达水平在检查的三个口腔粘膜活检时间点（感染后第2 - 4天、第14 - 21天和第70天）的每一个都升高。相比之下，进展更快的猕猴表现出淋巴结中这些细胞因子/趋化因子mRNA水平升高，与粘膜部位水平降低一致，并且引发有效抗SIV抗体反应的能力降低。这些数据提供了证据表明，一个强大的粘膜先天性/效应免疫反应是有益的慢病毒暴露后，然而，它是可能的，解剖位置和反应的时间需要协调，以允许有效的免疫反应能够延迟进展到猿艾滋病。