Murine cytomegalovirus infection down-regulates MHC class II expression on macrophages by induction of IL-10.
Murine cytomegalovirus infection down-regulates MHC class II expression on macrophages by induction of IL-10.
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DOI：
10.4049/jimmunol.162.11.6701
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发表时间：
1999-06
影响因子：
4.4
通讯作者：
Stella Redpath;Ana Angulo;N. R. Gascoigne;Peter Ghazal
中科院分区：
文献类型：
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作者：
Stella Redpath;Ana Angulo;N. R. Gascoigne;Peter Ghazal
疱疹病毒利用许多策略来削弱宿主的免疫反应。对于CMV，这包括避免NK清除和抑制MHC I类和II类递呈通路。在这项研究中，我们报道了小鼠巨细胞病毒(MCMV)在感染过程的非常早的时候特异性地引起宿主IL-10的过早和短暂的激活，导致MHC II类表面表达的显著和选择性的减少。IL-10的表达通常在对病原体的免疫反应中较晚，通过抑制炎性细胞因子的产生来抑制反应。在巨噬细胞的感染中，我们发现MCMV诱导IL-10的产生，导致细胞表面MHC-II类分子的表达早期和选择性地减少。IL-10的中和抗体或IL-10缺陷小鼠的巨噬细胞均不能抑制MHC-II类分子的表达。此外，感染MCMV的IL-10缺陷小鼠比正常小鼠更早和更强烈地诱导巨噬细胞MHC II类。综上所述，我们的结果表明，病毒诱导的IL-10自分泌途径在干扰素-γ刺激之前选择性地减少APC表面MHC-II类的表达起着至关重要的早期作用。
Herpesviruses utilize many strategies for weakening the host immune response. For CMV, this includes avoidance of NK clearance and inhibition of MHC class I and class II presentation pathways. In this study, we report that mouse CMV (MCMV) specifically causes a premature and transient activation of host IL-10 very early in the course of infection, resulting in a dramatic and selective reduction in MHC class II surface expression. The expression of IL-10 is normally late in the immune response to a pathogen, serving to dampen the response by suppression of the production of inflammatory cytokines. In infection of macrophages, we show that MCMV induces the production of IL-10, leading to an early and selective reduction in the expression of MHC class II on the surface of the cells. Inhibition of MHC class II expression was not observed in the presence of neutralizing Abs to IL-10 or in macrophages from IL-10-deficient mice. Moreover, MCMV-infected IL-10-deficient mice developed an early and significantly more robust macrophage MHC class II induction than normal mice. Altogether, our results demonstrate that viral induction of an IL-10 autocrine pathway plays an essential early role in selectively reducing MHC class II expression on the surface of APC prior to stimulation by IFN-gamma.