Potential Role of Interleukin-18 in the Immunopathogenesis of AIDS: Involvement in Fratricidal Killing of NK Cells
Potential Role of Interleukin-18 in the Immunopathogenesis of AIDS: Involvement in Fratricidal Killing of NK Cells
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DOI：
10.1128/jvi.02350-08
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发表时间：
2009-06-15
影响因子：
5.4
通讯作者：
Ahmad, Ali
中科院分区：
文献类型：
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作者：
Iannello, Alexandre;Samarani, Suzanne;Ahmad, Ali
我们先前已经表明，与HIV血清阴性的健康受试者相比，人类免疫缺陷病毒（HIV）感染者的循环白细胞介素-18（IL-18）浓度显著升高。在本研究中，我们研究了IL-18水平升高对自然杀伤（NK）细胞和艾滋病免疫发病机制的影响。我们在这里显示了IL-18浓度和感染者NK细胞的各种亚群的绝对数量之间的负相关性。重组人IL-18在体外引起人NK细胞系以及原代人NK细胞的死亡增加。IL-18介导的细胞死亡依赖于Fas-FasL相互作用和肿瘤坏死因子α。IL-18诱导NK细胞表达FasL，增加人FasL启动子的转录，降低NK细胞中Bcl-X-L的表达，并增加其对FasL介导的细胞死亡的敏感性。这些结果表明，增加IL-18浓度存在于HIV感染者的循环有助于艾滋病的免疫发病机制，通过改变NK细胞的稳态。
We had shown earlier that the concentrations of circulating interleukin-18 (IL-18) are increased significantly in human immunodeficiency virus (HIV)-infected persons compared to HIV-seronegative healthy subjects. In the present study, we investigated the consequences of these elevated levels of IL-18 on natural killer (NK) cells and the immunopathogenesis of AIDS. We show here an inverse correlation between IL-18 concentrations and absolute numbers of various subsets of NK cells in infected persons. Recombinant human IL-18 caused increased death of a human NK cell line, as well as of primary human NK cells in vitro. The IL-18-mediated cell death was dependent upon Fas-FasL interactions and tumor necrosis factor alpha. IL-18 induced the expression of FasL on NK cells, increased the transcription from the human FasL promoter, reduced the expression of Bcl-X-L in NK cells, and increased their sensitivity to FasL-mediated cell death. These results suggest that increased IL-18 concentrations present in the circulation of HIV-infected persons contribute to the immunopathogenesis of AIDS by altering NK cell homeostasis.