Plasma levels of bacterial DNA correlate with immune activation and the magnitude of immune restoration in persons with antiretroviral-treated HIV infection.

Plasma levels of bacterial DNA correlate with immune activation and the magnitude of immune restoration in persons with antiretroviral-treated HIV infection.
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DOI:
10.1086/597476
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发表时间:
2009-04-15
期刊:
The Journal of infectious diseases
影响因子:
--
通讯作者:
Brenchley JM
Brenchley JM
中科院分区:
其他
文献类型:
--
作者:
Jiang W;Lederman MM;Hunt P;Sieg SF;Haley K;Rodriguez B;Landay A;Martin J;Sinclair E;Asher AI;Deeks SG;Douek DC;Brenchley JM

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慢性HIV感染者血浆细菌脂多糖(LPS)水平升高的意义尚不明确。我们使用鲎试剂测定LPS水平,并通过定量聚合酶链反应对242名供体血浆样本中编码细菌核糖体16S RNA (16S rDNA)的DNA序列进行评估。人类免疫缺陷病毒(HIV)感染者血浆中16S rDNA水平显著高于未感染者,且与LPS水平相关。在抗逆转录病毒治疗期间,较高水平的16S rDNA与较高水平的T细胞激活和较低水平的CD4 T细胞恢复有关。抗逆转录病毒治疗降低但不能完全使血浆细菌16S rDNA水平正常化,这是胃肠道微生物易位的一个指标。治疗期间高水平的16S rDNA与CD4+ T淋巴细胞计数的减少密切相关,与血浆HIV RNA水平无关。这些发现与慢性HIV感染中微生物易位在免疫缺陷和T细胞稳态中的重要性是一致的。
The significance of elevated plasma levels of bacterial lipopolysaccharide (LPS) in persons with chronic HIV infection remains undefined. We measured LPS levels by use of limulus lysate assay, and DNA sequences encoding bacterial ribosomal 16S RNA (16S rDNA) were assessed by quantitative polymerase chain reactions in plasma samples obtained from 242 donors. Plasma levels of 16S rDNA were significantly higher in human immunodeficiency virus (HIV)–infected subjects than in uninfected subjects, and they correlated with LPS levels. Higher levels of 16S rDNA were associated with higher levels of T cell activation and with lower levels of CD4 T cell restoration during antiretroviral therapy. Antiretroviral therapy reduces but does not fully normalize plasma levels of bacterial 16S rDNA, an index of microbial translocation from the gastrointestinal tract. High levels of 16S rDNA during therapy are strongly associated with reduced increases in the CD4+ T lymphocyte count, irrespective of plasma HIV RNA levels. These findings are consistent with the importance of microbial translocation in immunodeficiency and T cell homeostasis in chronic HIV infection.
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