HIV infection induces age-related changes to monocytes and innate immune activation in young men that persist despite combination antiretroviral therapy
HIV infection induces age-related changes to monocytes and innate immune activation in young men that persist despite combination antiretroviral therapy
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DOI：
10.1097/qad.0b013e328351f756
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发表时间：
2012-04-24
期刊：
影响因子：
3.8
通讯作者：
Crowe, Suzanne M.
中科院分区：
文献类型：
--
作者：
Hearps, Anna C.;Maisa, Anna;Crowe, Suzanne M.
目的：比较 HIV 感染和健康老龄化对单核细胞表型和功能的影响，并确定 HIV 引起的年龄相关变化是否在抗逆转录病毒治疗个体中得到逆转。设计：对 45 岁或以下的病毒血症和病毒学抑制的 HIV 阳性男性以及年龄匹配的老年人（>= 65 岁）未感染 HIV 个体的单核细胞衰老标志物进行横断面研究。方法：单核细胞的年龄相关变化通过离体全血测定对 CD14(++)CD16(-) (CD14(+)) 和 CD14(可变)CD16(+) (CD16(+)) 亚群的表型和功能进行测量。通过 ELISA 测量与先天免疫激活相关的血浆标志物。 结果：年轻病毒血症 HIV 阳性男性的单核细胞与老年对照的单核细胞相似，并且在以下情况下显示 CD11b 表达增加（CD14(+) 和 CD16(+) 亚群上的 P < 0.0001），而 CD62L 和 CD115 的表达减少（CD14(+) 单核细胞上分别为 P = 0.04 和 0.001）。与年轻的未感染对照相比。这些变化也存在于病毒学受到抑制的年轻艾滋病毒阳性男性中。先天性免疫激活标志物新蝶呤、可溶性 CD163 和 CXCL10 在年轻病毒血症（全部 P < 0.0001）和病毒学抑制（分别为 P = 0.0005、0.003 和 0.002）HIV 阳性男性中均升高，抑制个体中的水平与老年对照中观察到的水平相似。与老年人一样，与年轻未感染对照相比，年轻 HIV 阳性男性的 CD14(+) 单核细胞表现出吞噬功能受损 (P = 0.007) 和端粒缩短 (P = 0.03)。结论：HIV 感染引起年轻 HIV 阳性男性单核细胞表型和功能的变化，与老年未感染者中观察到的变化相似，表明 HIV 可能会加速单核细胞的年龄相关变化。重要的是，这些缺陷在病毒学抑制的艾滋病毒阳性个体中持续存在。 (C) 2012 年 Wolters Kluwer Health 垂直条 Lippincott Williams & Wilkins
Objectives: To compare the impact of HIV infection and healthy ageing on monocyte phenotype and function and determine whether age-related changes induced by HIV are reversed in antiretroviral treated individuals.Design: A cross sectional study of monocyte ageing markers in viremic and virologically suppressed HIV-positive males aged 45 years or less and age-matched and elderly (>= 65 years) HIV-uninfected individuals.Methods: Age-related changes to monocyte phenotype and function were measured in whole blood assays ex vivo on both CD14(++)CD16(-) (CD14(+)) and CD14(variable)CD16(+) (CD16(+)) subsets. Plasma markers relevant to innate immune activation were measured by ELISA.Results: Monocytes from young viremic HIV-positive males resemble those from elderly controls, and show increased expression of CD11b (P < 0.0001 on CD14(+) and CD16(+)subsets) and decreased expression of CD62L and CD115 (P = 0.04 and 0.001, respectively, on CD14(+) monocytes) when compared with young uninfected controls. These changes were also present in young virologically suppressed HIV-positive males. Innate immune activation markers neopterin, soluble CD163 and CXCL10 were elevated in both young viremic (P < 0.0001 for all) and virologically suppressed (P = 0.0005, 0.003 and 0.002, respectively) HIV-positive males with levels in suppressed individuals resembling those observed in elderly controls. Like the elderly, CD14(+) monocytes from young HIV-positive males exhibited impaired phagocytic function (P = 0.007) and telomere-shortening (P = 0.03) as compared with young uninfected controls.Conclusion: HIV infection induces changes to monocyte phenotype and function in young HIV-positive males that mimic those observed in elderly uninfected individuals, suggesting HIV may accelerate age-related changes to monocytes. Importantly, these defects persist in virologically suppressed HIV-positive individuals. (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins