Department of Rheumatology and Inflammation Research, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
PLoS One. 2012;7(6):e38683. doi: 10.1371/journal.pone.0038683. Epub 2012 Jun 6.
Human herpesvirus type 6B (HHV-6B) is a strong inducer of IFN-alpha and has the capacity to promote Th1 responses and block Th2 responses in vitro. In this study we addressed whether inactivated HHV-6B can also induce IFN lambda responses and to what extent interferons alpha and lambda affect Th1/Th2 polarization. We show that inactivated HHV-6B induced IFN-lambda1 (IL-29) but not IFN-lambda2 (IL-28A) responses in plasmacytoid DC and that this induction was mediated through TLR9. We have previously shown that HHV-6B promotes Th1 responses and blocks Th2 responses in both humans and mice. We now show that neutralization of IFN-alpha but not IFN-lambda1 blocked the HHV-6B-induced enhancement of Th1 responses in MLR, but did not affect the HHV-6-induced dampening of Th2 responses. Similarly, blockage of TLR9 counteracted HHV-6Bs effects on the Th1/Th2 balance. In addition, IFN-alpha but not IFN-lambda1 promoted IFN-gamma production and blocked IL-5 and IL-13 production in purified CD4+ T-cells. The lack of effect of IFN-lambda1 correlated with the absence of the IFN-lambda receptor IL-28Ralfa chain on the cell surface of both resting and activated CD4+ T-cells. We conclude that inactivated HHV-6B is a strong inducer of IFN-lambda1 in plasmacytoid DC and that this induction is TLR9-dependent. However, human CD4+ T-cells do not express the IFN-lambda receptor and are refractory to IFN-lambda1 treatment. The HHV-6B-induced alterations in the Th1/Th2 balance are instead mediated mainly through TLR9 and IFN-alpha.
人类疱疹病毒 6B（HHV-6B）是干扰素-α的强烈诱导剂，具有在体外促进 Th1 反应和阻断 Th2 反应的能力。在这项研究中，我们研究了失活的 HHV-6B 是否也能诱导干扰素 λ 反应，以及干扰素 α 和 λ 对 Th1/Th2 极化的影响程度。我们表明，失活的 HHV-6B 诱导浆细胞样树突状细胞产生 IFN-λ1（IL-29），但不诱导 IFN-λ2（IL-28A）反应，这种诱导是通过 TLR9 介导的。我们之前已经表明，HHV-6B 在人和小鼠中均促进 Th1 反应并阻断 Th2 反应。我们现在表明，中和 IFN-α而不是 IFN-λ1 阻断了 HHV-6B 诱导的 MLR 中 Th1 反应的增强，但不影响 HHV-6 诱导的 Th2 反应的抑制。同样，阻断 TLR9 抵消了 HHV-6B 对 Th1/Th2 平衡的影响。此外，IFN-α而不是 IFN-λ1 促进了纯化的 CD4+T 细胞中 IFN-γ的产生，并阻断了 IL-5 和 IL-13 的产生。IFN-λ1 缺乏作用与静止和激活的 CD4+T 细胞表面缺乏 IFN-λ 受体 IL-28Ralfa 链有关。我们得出结论，失活的 HHV-6B 是浆细胞样树突状细胞中 IFN-λ1 的强烈诱导剂，这种诱导依赖于 TLR9。然而，人类 CD4+T 细胞不表达 IFN-λ 受体，对 IFN-λ1 治疗无反应。HHV-6B 诱导的 Th1/Th2 平衡改变主要通过 TLR9 和 IFN-α 介导。
