The immunoregulatory effects of CMV-infection in human fibroblasts and the impact on cellular senescence

Abstract

BackgroundAs a chronic antigenic stressor human Cytomegalovirus (CMV) contributes substantially to age-related alterations of the immune system. Even though monocytes have the greatest propensity for CMV-infection and seem to be an important host for the virus during latency, fibroblasts are also discussed to be target cells of CMV in vivo. However, little is known so far about general immunoregulatory properties of CMV in fibroblasts. We therefore investigated the immunoregulatory effects of CMV-infection in human lung fibroblasts and the impact on replicative senescence.FindingsWe observed that CMV-infection led to the induction of several immunoregulatory host cell genes associated with the innate and adaptive immune system. These were genes of different function such as genes regulating apoptosis, cytokines/chemokines and genes that are responsible for the detection of pathogens. Some of the genes upregulated following CMV-infection are also upregulated during cellular senescence, indicating that CMV causes an immunological phenotype in fibroblasts, which is partially reminiscent of replicative senescent cells.ConclusionIn summary our results demonstrate that CMV not only affects the T cell pool but also induces inflammatory processes in human fibroblasts.