Virus infection switches TLR-3-positive human neurons to become strong producers of beta interferon
Virus infection switches TLR-3-positive human neurons to become strong producers of beta interferon
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DOI：
10.1128/jvi.79.20.12893-12904.2005
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发表时间：
2005-10-01
影响因子：
5.4
通讯作者：
Lafon, M
中科院分区：
文献类型：
--
作者：
Préhaud, C;Mégret, F;Lafon, M
为了研究人类神经元对病毒感染产生先天免疫反应的能力，我们用狂犬病毒（RABV）和1型单纯疱疹病毒（HSV-1）感染了人类有丝分裂后神经元衍生细胞系NT2-N细胞。使用Affymetrix微阵列分析神经元基因表达的变化。采用双切断，RABV增加了228个基因的转录，HSV-1增加了263个基因的转录。这两种感染之间最显著的区别在于与免疫有关的基因。这些基因占rabv上调基因的24%，仅占hsv -1上调基因的4.9%。RABV感染后，上调最多的基因属于免疫簇，几乎完全包括β干扰素（ifn - β）原发性和继发性反应基因，以及趋化因子（CCL-5、CXCL-10）和炎症因子（白细胞介素6 [IL-6]、肿瘤坏死因子α、白细胞介素I α）基因。相比之下，HSV-1感染没有增加ifn - β基因转录，仅触发IL-6和干扰素调节因子1 mrna的产生。微阵列结果通过实时PCR、免疫细胞化学和酶联免疫吸附试验证实。发现人类神经元表达toll样受体3。它们在聚（I:C）处理后产生ifn - β，而不是脂多糖处理。因此，人类神经元可以对双链RNA产生先天免疫反应。这些观察结果坚定地证明，在没有神经胶质的情况下，人类神经元具有感知病毒感染的内在机制。
To study the capacity of human neurons to mount innate immunity responses to viral infections, we infected cells of a human postmitotic neuron-derivative cell line, NT2-N, with rabies virus (RABV) and herpes simplex type 1 (HSV-1). Changes in neuronal gene expression were analyzed by use of Affymetrix microarrays. Applying a twofold cutoff, RABV increased the transcription of 228 genes, and HSV-1 increased the transcription of 263 genes. The most striking difference between the two infections concerns genes involved in immunity. These genes represent 24% of the RABV-upregulated genes and only 4.9% of the HSV-1-upregulated genes. Following RABV infection, the most upregulated genes belong to the immunity cluster and included almost exclusively genes for beta interferon (IFN-beta) primary and secondary responses as well as genes for chemokines (CCL-5, CXCL-10) and inflammatory cytokines (interleukin 6 [IL-6], tumor necrosis factor alpha, interleukin I alpha). In contrast, HSV-1 infection did not increase IFN-beta gene transcripts and triggered the production of only IL-6 and interferon regulatory factor 1 mRNAs. The microarray results were confirmed by real-time PCR, immunocytochemistry, and enzyme-linked immunosorbent assay. Human neurons were found to express Toll-like receptor 3. They produced IFN-beta after treatment with poly(I:C) but not with lipopolysaccharide. Thus, human neurons can mount an innate immunity response to double-stranded RNA. These observations firmly establish that human neurons, in absence of glia, have the intrinsic machinery to sense virus infection.