Date Published: October 24, 2013
Publisher: Public Library of Science
Author(s): Melissa Swiecki, Yaming Wang, Susan Gilfillan, Marco Colonna, Blossom Damania.
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.
Most cells are able to produce type I interferons (IFN-I) in response to viruses, however, some cell types such as plasmacytoid dendritic cells (pDC) are more efficient than others. pDC detect RNA and DNA viruses through two endosomal sensors, Toll-like receptor (TLR) 7 and TLR9, respectively, which induce secretion of IFN-I through the MyD88-IRF7 signaling pathway –. Because of their capacity to produce IFN-I, as well as proinflammatory cytokines, and their ability to present antigens to T cells, pDC are thought to be important for promoting immune responses, particularly to viruses , .
In this study, we evaluated antiviral responses during local and systemic HSV infections in the presence and absence of pDC using CLEC4C-DTR Tg mice. We found that pDC have a negligible impact on viral burden, local IFN-I production and survival during vaginal HSV-2 infection and virus-specific CD8 T cell responses after subcutaneous HSV-1 infection. In contrast, pDC were essential for optimal IFN-I production, NK cell activation, CD8 T cell responses and survival following systemic HSV-2 and HSV-1 infections. These findings suggest that the contribution of pDC to antiviral immunity is dependent on the route of virus entry. Although pDC are often recruited to sites of infection and inflammation , , in homeostatic conditions they are mainly found in circulation and lymphoid tissues, which may explain why they have a more prominent role in controlling systemic viral infections. Indeed, it has been reported that following local infections with viruses such as Newcastle disease virus and vesicular stomatitis virus, macrophages are major sources of IFN-I and promote antiviral responses , .