Interleukin-32 isoforms: expression, interaction with interferon-regulated genes and clinical significance in chronically HIV-1-infected patients
Interleukin-32 isoforms: expression, interaction with interferon-regulated genes and clinical significance in chronically HIV-1-infected patients
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DOI：
10.1007/s00430-014-0329-2
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发表时间：
2014-06-01
影响因子：
5.4
通讯作者：
Scagnolari, Carolina
中科院分区：
文献类型：
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作者：
Monteleone, Katia;Di Maio, Pierluigi;Scagnolari, Carolina
鉴于越来越多的证据表明白细胞介素-32（IL-32）在对HIV-1感染的免疫应答中的作用及其与I型和III型干扰素（IFN）的相互作用，我们研究了未经治疗的慢性HIV-1感染患者和性别和年龄匹配的健康个体中IL-32亚型（α和非α）的基因表达。为了进一步表征IL-32的抗HIV特性和细胞因子与宿主抗病毒先天免疫应答的关系，我们评估了IL-32是否可以离体诱导抗病毒IFN诱导基因（ISG）的表达，即粘病毒抗性A（MxA）和载脂蛋白B mRNA编辑酶催化（APOBEC）3G和APOBEC 3F。我们还研究了体内IL-32（α和非α）mRNA水平是否与MxA和APOBEC 3G/3F相关。结果表明，IL-32（α和非α）mRNA水平显着高于HIV-1感染者比健康人。此外，IL-32（α和非α）mRNA水平与HIV RNA水平呈负相关，但与CD 4（+）T细胞计数无关。我们的离体研究揭示了在IL-32 γ处理外周血单核细胞后ISGs mRNA水平增加。有趣的是，在未经治疗的慢性HIV-1感染患者中，IL-32 α和IL-32非α的转录水平与MxA和APOBEC 3G/3F的转录水平之间存在显著的正相关性。总体而言，我们的研究结果表明，IL-32亚型在慢性HIV-1感染期间高度表达，并且IL-32可能在针对HIV-1的抗病毒免疫应答中发挥核心作用。
Given the growing evidence for a role of interleukin-32 (IL-32) in the immune response to HIV-1 infection and its interplay with type I and III interferons (IFNs), we studied the gene expression of IL-32 isoforms (alpha and non alpha) in untreated chronically HIV-1-infected patients and in gender- and age-matched healthy individuals. To further characterize both the anti-HIV properties of IL-32 and the cytokine's relationship with host antiviral innate immune responses, we evaluated whether IL-32 can induce ex vivo the expression of antiviral IFN-induced genes (ISGs), namely myxovirus resistance A (MxA), and apolipoprotein B mRNA-editing enzyme catalytic (APOBEC)3G and APOBEC3F. We also investigated whether in vivo IL-32 (alpha and non alpha) mRNA levels were correlated with those of MxA and APOBEC3G/3F. Results indicated that IL-32 (alpha and non alpha) mRNA levels were significantly higher in HIV-1-infected patients than in healthy individuals. Furthermore, IL-32 (alpha and non alpha) mRNA levels correlated negatively with HIV RNA levels, but not with the CD4(+) T-cell count. Our ex vivo studies disclosed that ISGs mRNA levels were increased after IL-32 gamma treatment of peripheral blood mononuclear cells. Interestingly, significant positive correlations were found between transcript levels of both IL-32 alpha and IL-32non alpha and those of MxA and APOBEC3G/3F in untreated chronically HIV-1-infected patients. Overall, our results demonstrated that IL-32 isoforms are highly expressed during chronic HIV-1 infection and that IL-32 could have a central role in the antiviral immune response against HIV-1.