Th207 - Heme Oxygenase 1 (HO-1) Expression in Dendritic Cells Promotes Antiviral Immunity Against Herpes Simplex Virus Skin Infection

Abstract Text: Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) infections are highly prevalent in the human population, producing a wide range of diseases that go from mild to life-threatening. These viruses infect epithelial cells and neurons where they establish latency, but also dendritic cells, key immune cells involved in the initiation and regulation of antiviral immunity. HSVs block DC maturation and function and ultimately leads to their apoptosis. Heme oxygenase-1 (HO-1) is an inducible host enzyme with increasingly reported antiviral activity. Thus, we sought to assess whether HO-1 modulates the function and viability of DCs upon infection with HSVs. Importantly, we found that HO-1 expression in HSV-inoculated DCs significantly recovers DC function, noteworthy cell viability and hampers viral egress. The stimulation of HO-1 expression in HSV-infected DCs promoted the expression of anti-inflammatory molecules in Dos and elicited the activation of virus-specific CD4+ T cells with regulatory (Treg) and Th17 phenotypes. Furthermore, stimulation of HO-1 expression in HSV-infected DCs transferred into mice favored their migration to the draining lymph nodes, the activation of virus-specific T cells and improved the outcome of HSV-1 skin infection. These findings suggest that HO-1 expression in DCs limits the deleterious effects of HSVs over these cells and induces a favorable virus-specific immune response in the skin against HSV-1.