HSV-1 induces macrophage activation and dysregulation in monocytes

Clinical cases of double infections by fungi and viruses are increasing, especially in immunocompromised hosts. To date, the biomolecular events that characterize the outcome of polymicrobic diseases remain poorly investigated and little is known on the mutual interactions occurring between pathogens. In order to investigate the interplay between microrganisms co-infecting macrophagic cells, we recently set up an in vitro model in which a monocytic cell line was infected with human herpesvirus 6 and C. neoformans. In the present work, we used an similar model to understand the molecular mechanisms underlying interactions between herpes simplex virus 1 (HSV-1) and C. albicans. The monocytic cell line THP-1 was infected with HSV-1 and, after an overnight incubation, cells were exposed to C. albicans. The cell response to the viral infection was evaluated as phagocytosis of C. albicans and killing of the ingested fungus. Moreover, a number of activation markers (CD38, CD69, CD95) and adhesion molecules (CD54, TLR-2, CD11b, CD106) was evaluated by FACS analysis in THP-1 cells. THP-1 cells infected with HSV-1 showed increased phagocytosis of C. albicans but reduced killing capability, suggesting that in the course of a double infection macrophages could contribute to yeast dissemination. Activation markers (CD38 and CD69) were found down expressed by FACS analysis in HSV-1-infected THP-1 cells, accounting for the failure in the antifungal activity.