HIV-1 exposed dendritic cells show increased pro-inflammatory cytokine production but reduced IL-1ra following lipopolysaccharide stimulation
HIV-1 exposed dendritic cells show increased pro-inflammatory cytokine production but reduced IL-1ra following lipopolysaccharide stimulation
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DOI：
10.1097/00002030-199910220-00003
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发表时间：
1999-10-22
期刊：
影响因子：
3.8
通讯作者：
Andersson, J
中科院分区：
文献类型：
--
作者：
Loré, K;Sönnerborg, A;Andersson, J
目的：树突状细胞 (DC) 是性传播 HIV-1 感染的潜在第一个靶细胞。它们还被认为是初始T细胞激活的核心，因此初始T细胞可能变得容易感染HIV-1。此外，活化的 DC 表达效应分子，这可能有助于 T 辅助细胞 (Th1/Th2) 特异性免疫反应的方向。方法：通过酶联免疫吸附测定 (ELISA) 和单细胞水平的原位免疫细胞化学检测来评估感染和未感染 HIV-1 的体外 DC 产生细胞因子和趋化因子的能力。采用荧光原位5'-核酸酶测定（FISNA）对HIV-1 gag阳性细胞进行定量评估。结果：嗜巨噬细胞的HIV-1有效感染20-40%的体外培养DC。然而，这种活性本身并不能诱导 DC 中可检测到的细胞因子或趋化因子蛋白表达。相反，与LPS刺激但未感染的DC培养物相比，脂多糖（LPS）刺激这些HIV-1感染的DC导致产生肿瘤坏死因子α（TNF-α）和白细胞介素（IL）1β的细胞水平显着增加，但产生IL-1受体拮抗剂（IL-1ra）的细胞频率降低（P < 0.05）。此外，在DC中检测到响应LPS和HIV-1加LPS的β-趋化因子[RANTES，巨噬细胞炎症蛋白(MIP)1α和1β]的大量产生。结论：这些发现表明HIV-1感染的DC可能具有增加的促炎活性。 TNF-α和IL-1β等细胞因子的产生增加以及IL-1ra的减少可能有助于增强旁观者T细胞中HIV-1的复制。 HIV-1感染者的Cram阴性细菌感染和肠道相关细菌易位也可能导致旁观者CD4 CD45RO T细胞中内毒素介导的HIV-1重新激活，这是由DC中促炎细胞因子产生增加引起的。 (C) 1999 年利平科特·威廉姆斯和威尔金斯。
Objectives: Dendritic cells (DC) are potential first target cells in sexually transmitted HIV-1 infection. They are also considered to be central in the activation of naive T cells, which thereupon can become permissive for HIV-I. In addition, activated DC express effector molecules, which likely contribute to the direction of T helper (Th1/Th2)-specific immune responses.Methods: The capacity of cytokine and chemokine production in in vitro DC infected and uninfected with HIV-1 was assessed by enzyme-linked immunosorbent assay (ELISA) and by in situ immunocytochemical detection at the single cell level. Fluorescent in situ 5'-nuclease assay (FISNA) was used for quantitative evaluation of HIV-1 gag-positive cells.Results: Macrophage-tropic HIV-1 effectively infected 20-40% of in vitro cultured DC. However, this activity alone did not induce detectable cytokine or chemokine protein expression in DC. In contrast, lipopolysaccharide (LPS) stimulation of these HIV-1-infected DC resulted in a significantly increased level of cells producing tumour necrosis factor alpha (TNF-alpha) and interleukin (IL) 1 beta but reduced frequencies of cells producing IL-1 receptor antagonist (IL-1ra) compared with the LPS-stimulated but uninfected DC cultures (P < 0.05). Furthermore, an extensive production of the beta-chemokines [RANTES, macrophage inflammatory proteins (MIP) 1 alpha and 1 beta] was detected in DC in response to both LPS and HIV-1 plus LPS.Conclusions: These findings indicate that HIV-I infected DC may have an increased proinflammatory activity. Elevated production of cytokines such as TNF-alpha and IL-1 beta and reduced IL-1ra may contribute to enhanced replication of HIV-1 in bystander T cells. Cram-negative bacterial infection and gut-associated bacterial translocation in HIV-1-infected individuals may also result in endotoxin-mediated reactivation of HIV-1 in bystander CD4 CD45RO T cells caused by the increased production of proinflammatory cytokines in DC. (C) 1999 Lippincott Williams & Wilkins.