HSV-1 induces dysregulation of monocyte anticandida functions

Clinical cases of double infections by fungi and viruses are increasing, especially in immunocompromised hosts. To date, the biomolecular events characterizing the outcome of polymicrobic diseases remain poorly investigated: little is known on the mutual interactions occurring between pathogens and on their concomitant, either synergistic or antagonistic, effects. In order to investigate the interplay occurring between pathogens in the course of double infections, we set up an in vitro model in which the monocytic cell line THP-1, was infected with HSV-1 and then exposed to Candida albicans. The effects of HSV-1 infection on macrophages were measured as capability to alter macrophage-mediated effector functions, namely phagocytosis and killing of Candida, and as gene and protein expression by FACS and RNA microarrays. Phagocytosis of Candida by THP-1 cells was significantly increased when macrophages were infected with HSV-1. Conversely, antifungal activity was impaired in HSV-1 infected macrophages at 6 hours after infection with Candida. FACS analysis of protein expression revealed a significant downregulation of TLR2 and TLR4, important molecules involved in fungi recognition and increase in the number of apoptotic cells. Gene expression profile disclosed a huge decrease in gene presence in HSV-1 infected macrophage (40% of gene presence in uninfected cells vs 20% in infected cells). The analysis of gene clusters showed a downregulation of genes involved in opsonized phagocytosis and intracellular killing, of many adhesion molecules and of TLR2; on the contrary, several lectin receptor genes (involved in Candida adhesion and phagocytosis) and apoptosis genes were significantly up-regulated.