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
Millennium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago 8331150, Chile.
Millennium Institute on Immunology and Immunotherapy, Departamento de Ciencias Biológicas, Facultad de Ciencias de la Vida, Universidad Andrés Bello, Santiago 8370133, Chile.
Antioxidants (Basel). 2023 May 29;12(6):1170. doi: 10.3390/antiox12061170.
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.
1型单纯疱疹病毒（HSV-1）和2型单纯疱疹病毒（HSV-2）感染在人群中高度流行，可引发从轻度到危及生命的疾病。这些病毒会干扰树突状细胞（DC）的功能和活力，而树突状细胞是启动和调节宿主抗病毒免疫反应的专职抗原呈递细胞。血红素加氧酶-1（HO-1）是一种可诱导的宿主酶，据报道其在上皮细胞和神经元中对单纯疱疹病毒具有抗病毒活性。在此，我们试图评估HO-1在DC感染HSV-1或HSV-2后是否会调节其功能和活力。我们发现，在接种HSV的DC中刺激HO-1表达可显著恢复这些细胞的活力并阻碍病毒释放。此外，受刺激表达HO-1的HSV感染的DC促进了抗炎分子如程序性死亡受体1（PDL-1）和白细胞介素-10（IL-10）的表达，以及具有调节性（Treg）、辅助性T细胞17（Th17）和Treg/Th17表型的病毒特异性CD4 T细胞的活化。此外，受刺激表达HO-1的HSV感染的DC随后转移到小鼠体内，可促进病毒特异性T细胞的活化，并改善HSV-1皮肤感染的结果。这些发现表明，刺激DC中HO-1的表达可限制HSV对这些细胞的有害影响，并在皮肤中诱导针对HSV-1的有利的病毒特异性免疫反应。
