title: Murine cytomegalovirus infection directs macrophage differentiation into a pro-inflammatory immune phenotype: implications for atherogenesis.
abstract: 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.
authors.affiliation: Department of Medical Microbiology, University Hospital Maastricht, P. Debyelaan 25, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands. ivl@lmib.azm.nl
authors.forename: Inge
authors.initials: I
authors.lastname: Vliegen
authors.forename: Adrian
authors.initials: A
authors.lastname: Duijvestijn
authors.forename: Frank
authors.initials: F
authors.lastname: Stassen
authors.forename: Cathrien
authors.initials: C
authors.lastname: Bruggeman
mesh_terms: D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology*; D002454:Cell Differentiation; D016207:Cytokines / Q000378:metabolism; D006566:Herpesviridae Infections / Q000150:complications* / Q000276:immunology / Q000821:virology; D007249:Inflammation; D008262:Macrophage Activation; D017737:Macrophages, Peritoneal / Q000166:cytology* / Q000276:immunology; D008297:Male; D051379:Mice; D018146:Muromegalovirus / Q000276:immunology*
chemical_list: D016207:Cytokines