Human herpesvirus-6 dysregulates monocyte-ediated anticryptococcal defences.

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, is exposed to Cryptococcus neoformans (Cn) and Human Herpesvirus 6 (HHV-6). Cn and HHV-6, both highly neurotropic, can cause serious diseases of the central nervous system and have monocytes, among other cell types, as target cells, causing alteration of their secretion pattern. Here, we show that, unlike THP-1 cells exposed to cell-free virus inocula, THP-1 exposed to HHV-6 producing lymphocytes exhibit augmented phagocytosis against Cn. The phenomenon occurs after 24 hours of monocyte/lymphocyte co-culture and it is independent of direct cell-to-cell contact. Moreover, in the presence of HHV-6, THP-1 cells express enhanced secretory responses but reduced capability to counteract fungal infection: the better ingestion by monocytes is followed by facilitated fungal survival and replication. These data provide initial in vitro evidence that HHV-6 may dysregulate monocyte-mediated anticryptococcal defences with an overall pro-cryptococcus result.