Vliegen Inge, Duijvestijn Adrian, Stassen Frank, Bruggeman Cathrien
Department of Medical Microbiology, University Hospital Maastricht, P. Debyelaan 25, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands.
Microbes Infect. 2004 Oct;6(12):1056-62. doi: 10.1016/j.micinf.2004.05.020.
We have previously demonstrated that mouse cytomegalovirus (MCMV) aggravates atherosclerosis in apolipoprotein E knockout (apoE(-/-)) mice, most likely by enhancing both systemic and local (e.g. in the vascular wall) cytokine production. However, until now it was unclear which cell type is responsible for this enhanced pro-inflammatory cytokine production. In this study we focused on the macrophage (mPhi), which besides being an important source of such cytokines, is known to be an important player in both atherosclerosis and viral clearance. We investigated whether MCMV could induce a pro-inflammatory immune mPhi phenotype, which ultimately may contribute to the development of atherosclerosis. To this end, peritoneal exudate cells (PEC) were elicited in apoE(-/-) mice by either MCMV or thioglycolate injection, and mPhi were phenotyped at 1 week post-intraperitoneal injection. MCMV-induced peritoneal mPhi contained MCMV DNA but had limited MCMV mRNA expression, indicating latent infection. These mPhi showed increased production of interferon-gamma (IFNgamma), exclusive production of interleukin-18 (IL-18) and increased expression of major histocompatibility complex (MHC) class II, CD40, CD80 and CD86, when compared with thioglycolate-induced mPhi. From these results, we conclude that intraperitoneal injection of MCMV induces an immune-responsive exudate in which at 7 days post-infection, MCMV-infected mPhi express a pro-inflammatory immune phenotype. As such, the MCMV-induced mPhi may be an important player in aggravating atherosclerosis through systemic and/or local immune activation.
我们先前已经证明，小鼠巨细胞病毒（MCMV）会加重载脂蛋白E基因敲除（apoE(-/-)）小鼠的动脉粥样硬化，很可能是通过增强全身和局部（如血管壁）细胞因子的产生来实现的。然而，直到现在还不清楚哪种细胞类型负责这种促炎细胞因子产生的增加。在本研究中，我们聚焦于巨噬细胞（mPhi），它除了是此类细胞因子的重要来源外，还已知在动脉粥样硬化和病毒清除过程中都发挥着重要作用。我们研究了MCMV是否能诱导促炎免疫性mPhi表型，这最终可能有助于动脉粥样硬化的发展。为此，通过注射MCMV或巯基乙酸盐在apoE(-/-)小鼠中诱导产生腹腔渗出细胞（PEC），并在腹腔注射后1周对mPhi进行表型分析。MCMV诱导的腹腔mPhi含有MCMV DNA，但MCMV mRNA表达有限，表明存在潜伏感染。与巯基乙酸盐诱导的mPhi相比，这些mPhi显示出干扰素-γ（IFNγ）产生增加、白细胞介素-18（IL-18）单独产生以及主要组织相容性复合体（MHC）II类、CD40、CD80和CD86表达增加。从这些结果中，我们得出结论，腹腔注射MCMV会诱导一种免疫反应性渗出物，在感染后7天时，MCMV感染的mPhi表达促炎免疫表型。因此，MCMV诱导的mPhi可能通过全身和/或局部免疫激活在加重动脉粥样硬化过程中发挥重要作用。
