Herpes simplex virus (HSV) is
a DNA virus with tropism for infecting skin and mucosal epithelia during the lytic stages of its complex life cycle. The immune system has evolved a multitude of strategies to respond to primary HSV
infections. These include rapid innate immune responses largely driven by pattern recognition systems and protective anti-viral immunity. Dendritic cells (DC) represent a versatile and heterogenic group of antigen presenting cells that are important for pathogen recognition at sites of
infection and for priming of protective HSV-specific T cells. Here we will review the current knowledge on the role of DCs in the host immune response to primary HSV
infection. We will discuss how DCs integrate viral cues into effective innate immune responses, will dissect how HSV
infection of DCs interferes with their capacity to migrate from sites of
infection to the draining lymph nodes and will outline how migratory DCs can make
antigens available to lymph node resident DCs. The role of distinct DC subsets and their relevant contribution to antigen presentation on MHC class I and
MHC class II molecules will be detailed in the context of T cell priming in the lymph node and the elicitation of effector function in infected tissues. An improved understanding of the fundamental mechanisms of how DCs recognize HSV, process and present its
antigens to naïve and effector T cells will not only assist in the improvement of
vaccine-based preventions of this important
viral disease, but also serves as a paradigm to resolve basic immunological principles.