MICROBIAL TRANSLOCATION & ALTERATIONS IN GUT MICROBIOMES IN HIV INFECTED CHILDREN

微生物易位

基本信息

批准号：
8516443
负责人：
Charles DeBeaux Mitchell
金额：
$ 34.61万
依托单位：
UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-01 至 2016-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8516443
关键词：
Adult Affect Age Age-Months Aliquot Automobile Driving Bacteria Bacterial Translocation Biological Assay Biological Markers Blood Circulation CCR5 gene CD14 gene CD8-Positive T-Lymphocytes CD8B1 gene Cell surface Child Chronic Clinical Communities Control Groups DNA Data Disease Disease Progression Enteral Feces Freezing Genome Genomics Growth HIV HIV Infections HIV-1 HLA-DR Antigens Highly Active Antiretroviral Therapy Human Immunosuppression Infant Infection Lipopolysaccharides Lymphocyte Macaca Measurable Measurement Measures Newly Diagnosed Newly Diagnosed Disease Pathogenesis Patients Perinatal Phylogenetic Analysis Plasma Population Recruitment Activity Regimen Relative (related person)Ribosomal DNA Specimen Staging T memory cell T-Cell Depletion T-Lymphocyte Testing Tissues Trees adaptive immunity antiretroviral therapy base gut microbiota immune activation microbial microbial community microbiome therapeutic target

项目摘要

DESCRIPTION (provided by applicant): HIV is now known to induce massive depletion of CD4+,CCR5+, memory T cells in the Gut Associated Lymphocyte Tissue (GALT) in macaques and humans within weeks following primary infection. Brenchley et al recently proposed that the microbial translocation of bacterial products into the systemic circulation from the gut in the wake of this massive T cell depletion may be a primary factor driving the persistent immune activation which characterizes chronic HIV infection. Most of the data supporting this hypothesis is cross-sectional and was obtained from adult patients. This study will determine whether there is a longitudinal correlation between increased levels of markers of microbial translocation and persistent immune activation in perinatally infected children. More specifically, it will determine whether increased circulating levels of lipopolysaccaride (LPS) and 16Sribosomal DNA(2 bacterial products) correlate with increased immune activation as evidenced by enhanced expression of the following markers: CD8+CD38+HLA-DR+, CD8+, CD38+, CD8+ HLA-DR+ T cells, and soluble CD14. Any specimen that has measurable 16SrDNA will also undergo qualitative 16SrRNA genomic amplification to determine what bacterial genus/species are being translocated. It will also determine whether there is a decline in the levels of these markers of microbial translocation which correlates with the decline in immune activation following the initiation of antiretroviral therapy. Recent evidence has also suggested that disturbances in the bacterial gut flora adversely affect adaptive immunity. To investigate this possibility which might further exacerbate the effects of microbial translocation by favoring the growth of more pathogenic species versus the usual symbiotic flora, this study will also determine whether there are significant differences in the proportions of major bacterial divisions comprising the enteric flora of HIV infected versus HIV uninfected children using the same 16SrRNA genomic amplification to characterize the microbial flora. If a correlation between the markers of microbial translocation and immune activation is confirmed and alterations in the microbial community that comprises the gut flora is detected, then a greater understanding of HIV pathogenesis may be gained and another potential therapeutic target identified; one that might allow us to disrupt the continuing cycle of immune activation that promotes HIV disease progression.

描述（由申请人提供）：现在已知HIV在猕猴和人类初期感染后几周内诱导CD4+，CCR5+，肠道相关淋巴细胞组织（GALT）中的记忆T细胞的大量耗竭。 Brenchley等人最近提出，在这种大规模T细胞耗竭后，细菌产物从肠道中从肠道中的微生物易位可能是驱动持续性免疫激活的主要因素，表征了慢性HIV感染。支持该假设的大多数数据是横断面的，是从成年患者那里获得的。这项研究将确定微生物易位标记水平的增加与围产期感染儿童的持续免疫激活之间是否存在纵向相关。更具体地说，它将确定脂多藻剂（LPS）（LPS）和16sribosomal DNA（2种细菌产物）是否增加与免疫激活相关的循环水平是否增加，这是由以下标记的增强表达：CD8+CD38+CD38+HLA+HLA-DR+，CD38+，CD38+，CD38+，CD38+HLA+HLA+HLA+tla和SOLU和SOLU和SOLU和SOLU和SOLU和SOLU和SOLU和SOLU和SOLU和SOLU和SOLU。任何具有可测量16srDNA的标本还将经历定性16sRRNA基因组扩增，以确定哪些细菌属/物种正在易位。它还将确定这些微生物易位标记的水平是否有所下降，这与抗逆转录病毒疗法开始后免疫激活的下降相关。最近的证据还表明，细菌肠道菌群中的干扰会对适应性免疫产生不利影响。 To investigate this possibility which might further exacerbate the effects of microbial translocation by favoring the growth of more pathogenic species versus the usual symbiotic flora, this study will also determine whether there are significant differences in the proportions of major bacterial divisions comprising the enteric flora of HIV infected versus HIV uninfected children using the same 16SrRNA genomic amplification to characterize the microbial flora.如果确认微生物易位标记和免疫激活之间的相关性，并且检测到构成肠道菌群的微生物群落的改变，则可以获得对HIV发病机理的更多了解，并确定另一个潜在的治疗靶标；一种可能使我们可以破坏促进HIV疾病进展的免疫激活的持续循环。