Differential expression of IFN-α and TRAIL/DR5 in lymphoid tissue of progressor versus nonprogressor HIV-1-infected patients
Differential expression of IFN-α and TRAIL/DR5 in lymphoid tissue of progressor versus nonprogressor HIV-1-infected patients
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DOI：
10.1073/pnas.0600363103
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发表时间：
2006-05-02
影响因子：
11.1
通讯作者：
Shearer, GM
中科院分区：
文献类型：
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作者：
Herbeuval, JP;Nilsson, J;Shearer, GM
CD4(+) T细胞的损失，HIV发病的标志，被认为部分是由于细胞凋亡。我们最近报道了由hiv -1激活的浆细胞样树突状细胞（pDCs）产生的ifn - α通过tnf相关凋亡诱导配体(TRAIL)/死亡受体（DR）5途径促进CD4(+) T细胞凋亡。在这里，我们发现hiv -1诱导的细胞内IFN- α在pDCs中的表达与体内和体外pDCs中IFN调节因子7和MyD88的表达增加相耦合。与非进展性（HIVNP） HIV-1疾病和未感染对照相比，进展性（hiv - prog）患者淋巴样扁桃体组织（LT）中IFN-a的表达增加。来自HIVprog的LT比来自HIVNP或对照组的LT表现出更高的TRAIL和DR5 mRNA水平。LT中TRAIL mRNA水平与血浆病毒载量相关。我们发现HIV-1在LT中诱导ifn - α和TRAIL/DR5凋亡通路，提示这些细胞因子在HIV-1免疫发病机制中的作用。
Loss of CD4(+) T cells, the hallmark of HIV pathogenesis, was suggested to be partly due to apoptosis. We recently reported that IFN-alpha produced by HIV-1-activated plasmacytoid dendritic cells (pDCs) contributes to CD4(+) T cell apoptosis by the TNF-related apoptosis-inducing ligand (TRAIL)/death receptor (DR)5 pathway. Here, we show that HIV-1-induced intracellular expression of IFN-alpha in pDCs is coupled to increased expression of IFN regulatory factor 7 and MyD88 by pDCs in vivo and in vitro. Expression of IFN-a was increased in lymphoid tonsillar tissue (LT) of patients with progressive (HIVprog) compared with nonprogressive (HIVNP) HIV-1 disease and to uninfected controls. LT from HIVprog exhibited higher TRAIL and DR5 mRNA levels than LT from HIVNP or controls. TRAIL mRNA levels in LT correlated with plasma viral load. We show that HIV-1 induces IFN-alpha and the TRAIL/DR5 apoptotic pathway in LT, suggesting a role for these cytokines in HIV-1 immunopathogenesis.