Heme Oxygenase-1 Expression in Dendritic Cells Contributes to Protective Immunity against Herpes Simplex Virus Skin Infection

Tognarelli Eduardo I.; Duarte, Luisa F.; Farías , Mónica A.; Cancino, Felipe A.; Corrales Nicolás; Ibáñez, Francisco J.; Riedel, Claudia A; Bueno, Susan M.; Kalergis, Alexis M; González Pablo A.

Keywords: dendritic cells, heme oxygenase-1, skin infection, th17, adaptive response, treg, herpes simplex virus, antiviral drug, Treg/Th17


Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) infections are highly prevalent in the human population and produce mild to life-threatening diseases. These viruses interfere with the function and viability of dendritic cells (DCs), which are professional antigen-presenting cells that initiate and regulate the host’s antiviral immune responses. Heme oxygenase-1 (HO-1) is an inducible host enzyme with reported antiviral activity against HSVs in epithelial cells and neurons. Here, we sought to assess whether HO-1 modulates the function and viability of DCs upon infection with HSV-1 or HSV-2. We found that the stimulation of HO-1 expression in HSV-inoculated DCs significantly recovered the viability of these cells and hampered viral egress. Furthermore, HSV-infected DCs stimulated to express HO-1 promoted the expression of anti-inflammatory molecules, such as PDL-1 and IL-10, and the activation of virus-specific CD4+ T cells with regulatory (Treg), Th17 and Treg/Th17 phenotypes. Moreover, HSV-infected DCs stimulated to express HO-1 and then transferred into mice, promoted the activation of virus-specific T cells and improved the outcome of HSV-1 skin infection. These findings suggest that stimulation of 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.

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Título de la Revista: ANTIOXIDANTS
Volumen: 12
Número: 6
Fecha de publicación: 2023
Página de inicio: 1170
Idioma: Inglés
URL: https://www.mdpi.com/2076-3921/12/6/1170


Notas: Antioxidants, an international, peer-reviewed Open Access indexed in Web of Science™ (WoS).