Dendritic cell function and resistance to cutaneous HSV-1 infections

• Published in: Journal of neurovirology 2006-05, Vol.12, p.38-38
• Main Authors: Kassim, SH, Zhao, Xiangyi, Jennings, SR
• Format: Article
• Language: English
• Subjects: Herpes simplex virus 1
• ISSN: 1355-0284

The immune system plays a particularly important role in controlling HSV-1 infection in both the nervous system and periphery. Innate mechanisms, including early IFN production and natural killer (NK) cell activation, represent the first line of defense against infection, limiting viral replication and spread before the more specific acquired CD8 T cell immune response is activated and optimal viral clearance achieved. The innate and acquired immune responses are ultimately linked together during antigen presentation amidst the inflammatory cytokine milieu generated during the innate immune response in the draining lymph nodes. Of professional antigen-presenting cells (APCs), dendritic cells (DCs) are thought to be particularly important links between the innate and adaptive immune responses against many pathogens. The role of DCs as mediators of resistance to HSV-1 infection was investigated using CD11c-diphtheria toxin (DT) receptorgreen fluorescent protein transgenic mice, in which DCs can be transiently depleted in vivo by treatment with low doses of DT. We show that ablation of DCs led to enhanced susceptibility to HSV-1 infection in the highly resistant C57BL/6 mouse strain. Specifically, we showed that the depletion of DCs lead to increased viral spread into the nervous system, resulting in an increased rate of morbidity and mortality. Furthermore, we showed that ablation of DCs impaired the optimal activation of NK cells, CD4+ and CD8+ T cells in response to HSV-1. These data demonstrated that DCs were essential not only in the optimal activation of the acquired T cell response to HSV-1, but that DCs were crucial for innate resistance to HSV-1 infection.