Impact of HIV Infection and Anti-Retroviral Therapy on the Immune Profile of and Microbial Translocation in HIV-Infected Children in Vietnam.

Impact of HIV Infection and Anti-Retroviral Therapy on the Immune Profile of and Microbial Translocation in HIV-Infected Children in Vietnam.
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DOI:
10.3390/ijms17081245
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发表时间:
2016-08-02
影响因子:
5.6
通讯作者:
Ichimura H
Ichimura H
中科院分区:
生物学2区
文献类型:
--
作者:
Bi X;Ishizaki A;Nguyen LV;Matsuda K;Pham HV;Phan CT;Ogata K;Giang TT;Phung TT;Nguyen TT;Tokoro M;Pham AN;Khu DT;Ichimura H

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CD4+ t淋巴细胞破坏、微生物易位和全身免疫激活是人类免疫缺陷病毒1型(HIV)感染的主要发病机制。为了研究艾滋病毒感染和抗逆转录病毒治疗(ART)对艾滋病毒感染儿童免疫特征和微生物易位的影响,在越南招募了60名艾滋病毒垂直感染儿童(31名未接受ART治疗:HIV(+), 29名接受ART治疗:ART(+))和20名2-12岁的艾滋病毒未感染儿童(HIV(-)),对他们的血液样本进行了免疫学和细菌学分析。在HIV(+)儿童中,CD4+细胞总数及其亚群(1型辅助性t细胞(Th1)/Th2/Th17)计数与年龄呈负相关(均p < 0.05),而调节性t细胞(Treg)计数和CD4/CD8比值逐渐降低,CD38+HLA(人白细胞抗原)- dr +CD8+-(活化CD8+)细胞百分比和血浆可溶性CD14 (sCD14,单核细胞活化标志物)水平在2岁时明显高于HIV(-)儿童;CD4/CD8比值与血浆HIV RNA载量和CD8+细胞激活状态呈负相关。在接受ART(+)治疗的儿童中,CD4+细胞总数和Th2/Th17/ treg亚群计数以及CD4/CD8比值逐渐升高,估计ART正常化周期为4.8-8.3年,而Th1计数和CD8+细胞激活状态在ART开始后1年内恢复正常。即使在抗逆转录病毒治疗开始后,sCD14水平仍然很高。hiv感染和未感染儿童血液中细菌16S/23S核糖体DNA/RNA的检测频率无差异。因此,在儿童中,HIV感染导致Treg计数迅速下降,CD8+细胞和单核细胞早期活化,ART诱导Th1快速恢复和CD8+细胞早期活化正常化,但对单核细胞活化影响不大。因此,CD4/CD8比值可以作为ART监测的额外标记。
CD4+ T-lymphocyte destruction, microbial translocation, and systemic immune activation are the main mechanisms of the pathogenesis of human immunodeficiency virus type 1 (HIV) infection. To investigate the impact of HIV infection and antiretroviral therapy (ART) on the immune profile of and microbial translocation in HIV-infected children, 60 HIV vertically infected children (31 without ART: HIV(+) and 29 with ART: ART(+)) and 20 HIV-uninfected children (HIV(−)) aged 2–12 years were recruited in Vietnam, and their blood samples were immunologically and bacteriologically analyzed. Among the HIV(+) children, the total CD4+-cell and their subset (type 1 helper T-cell (Th1)/Th2/Th17) counts were inversely correlated with age (all p < 0.05), whereas regulatory T-cell (Treg) counts and CD4/CD8 ratios had become lower, and the CD38+HLA (human leukocyte antigen)-DR+CD8+- (activated CD8+) cell percentage and plasma soluble CD14 (sCD14, a monocyte activation marker) levels had become higher than those of HIV(−) children by the age of 2 years; the CD4/CD8 ratio was inversely correlated with the plasma HIV RNA load and CD8+-cell activation status. Among the ART(+) children, the total CD4+-cell and Th2/Th17/Treg-subset counts and the CD4/CD8 ratio gradually increased, with estimated ART periods of normalization being 4.8–8.3 years, whereas Th1 counts and the CD8+-cell activation status normalized within 1 year of ART initiation. sCD14 levels remained high even after ART initiation. The detection frequency of bacterial 16S/23S ribosomal DNA/RNA in blood did not differ between HIV-infected and -uninfected children. Thus, in children, HIV infection caused a rapid decrease in Treg counts and the early activation of CD8+ cells and monocytes, and ART induced rapid Th1 recovery and early CD8+-cell activation normalization but had little effect on monocyte activation. The CD4/CD8 ratio could therefore be an additional marker for ART monitoring.
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