Modification of Monocyte Count and Subsets During Human Cytomegalovirus Replication in vivo and Glucocorticoid Therapy

Abstract

It has recently been discovered that mere cell contact by human cytomegalovirus (CMV) particles leads to profound modulation of cellular gene expression. Reduced monocyte human leukocyte antigen (HLA-DR) expression is a novel biomarker of severity and outcome in many diseases. Modulation of CD14 protein by CMV was shown in vitro, but little is known about the phenomenon in vivo (during active cytomegalovirus disease). Therefore, we investigated monocyte CD14 and HLA-DR expression in CMV infected patients in relation to logarithmic phase of infectious process. Samples from patients with active CMV replication (exponential growth of CMV viremia) were tested. After CD45/SSC gating monocyte CD14 and HLA-DR expression were determined by double-color flow-cytometry. Significant monocytosis and poor correlation between CMV replication and CD14+HLA-DR(-) cells prompted CD14 investigation. During logarithmic phase of CMV infection increased count and percentage of CD14low monocytes were observed which correlated with viral replication in several clinical situations except when there was a rapid recovery without relapse. Furthermore, most of CD14low monocytes are HLA-DR+. The increase of CD14low monocytes is also observed under the influence of high dose of glucocorticoids (20 mg of dexamethasone). The reduction in CD14 induced by CMV and dexamethasone indicates that the monocyte balance is disturbed between the classical and non-classical phenotype. A high percentage of CD14lowHLA-DR+ probably gives rise to adaptive and a decrease of innate immune response. In light of the logarithmic increase of viral load (with exponent between 3,23 and 5,77), high monocytosis above 1200 / µl is a hallmark of CMV replication.