Plasmacytoid Dendritic Cells Contribute to Systemic but Not Local Antiviral Responses to HSV Infections

Abstract

Plasmacytoid dendritic cells (pDC) produce type I interferons (IFN-I) and proinflammatory cytokines in response to viruses; however, their contribution to antiviral immunity in vivo is unclear. In this study, we investigated the impact of pDC depletion on local and systemic antiviral responses to herpes simplex virus (HSV) infections using CLEC4C-DTR transgenic mice. We found that pDC do not appear to influence viral burden or survival after vaginal HSV-2 infection, nor do they seem to contribute to virus-specific CD8 T cell responses following subcutaneous HSV-1 infection. In contrast, pDC were important for early IFN-I production, proinflammatory cytokine production, NK cell activation and CD8 T cell responses during systemic HSV-2 and HSV-1 infections. Our data also indicate that unlike pDC, TLR3-expressing cells are important for promoting antiviral responses to HSV-1 regardless of the route of virus administration.

Author Summary

Herpes simplex viruses (HSV) cause a variety of diseases in human from the common cold sore to more severe illnesses such as pneumonia, herpes simplex keratitis, genital herpes and encephalitis. HSV are large double-stranded DNA viruses that infect epithelial or epidermal cells before establishing a latent infection in sensory neurons. Both innate and adaptive immune responses are necessary for limiting viral replication and maintaining latency. Viral detection through distinct pathogen recognition pathways triggers several signaling cascades that lead to the production of proinflammatory cytokines and type I interferons, which establish inflammation, confer an antiviral state and promote immune responses. Our study provides new insights into the cell types and pathogen recognition pathways involved in antiviral defense to HSV at local and systemic barriers and thus, might facilitate the development of novel strategies to treat HSV infections.