Herpes simplex virus type 1 dysregulates anti-fungal defenses preventing monocyte activation and downregulating toll-like receptor-2

We investigated the interplay occurring between pathogens in the course of dual infections, using an in vitro model inwhich the THP-1 monocytic cell line is first infectedwith HSV-1 and then exposed to Ca or Cn. These three pathogens share some pathogenic features: they cause opportunistic infections, target macrophages and are neurotropic. Here, we show that HSV-1-infected THP-1 cells exhibited augmented phagocytosisagainstthetwoopportunisticfungibutreducedcapabilityto counteractfungal infection:the better ingestion bymonocytes was followed by facilitated fungal survival and replication. Reduced IL-12 productionwas also observed.Cytofluorimetric analysis showed that HSV-1-infectedmonocytes exhibit: (i) downregulated TLR-2 and TLR-4, critical structures in fungal recognition; (ii) reduced expression of CD38 and CD69, known to be important markers ofmonocyte activation; and (iii) enhanced expression of apoptosis and necrosis markers, in the absence of altered cell proliferation. Overall, these findings imply that HSV-1 infection prevents monocyte activation, thus leading to a significant dysfunction of the monocyte-mediated anti-Candida response; HSV-1 induced apoptosis and necrosis of monocytes further contribute to this impairment.