Skin-derived dendritic cells (DCs) include Langerhans cells, classical dermal DCs and a langerin-positive CD103(+) dermal subset. We examined their involvement in the presentation of skin-associated viral and self antigens. Only the CD103(+) subset efficiently presented antigens of herpes simplex virus type 1 to naive CD8(+) T cells, although all subsets presented these antigens to CD4(+) T cells. This showed that CD103(+) DCs were the migratory subset most efficient at processing viral antigens into the major histocompatibility complex class I pathway, potentially through cross-presentation. This was supported by data showing only CD103(+) DCs efficiently cross-presented skin-derived self antigens. This indicates CD103(+) DCs are the main migratory subtype able to cross-present viral and self antigens, which identifies another level of specialization for skin DCs.

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Despite its potential for involvement in viral immunity, little evidence links TLR3 to adaptive antiviral responses. Here we show that TLR3 is required for the generation of CD8 T cell immunity to HSV-1. The magnitude of the gB-specific CD8 T cell response after flank infection by HSV-1 was significantly reduced in mice lacking TIR domain-containing adaptor-inducing IFN-β or TLR3, but not MyD88. Impaired CTL induction was evident in chimeric mice lacking TLR3 in bone marrow (BM)-derived cells. Among the dendritic cell subsets, TLR3 was expressed by CD8α+ dendritic cells, known to be involved in priming HSV-1–specific CD8 T cells. Use of mixed BM chimeras revealed that TLR3 and the MHC class I-restriction element must be expressed by the same BM-derived cell for effective priming. These data imply that a cognate linkage between TLR3 and MHC class I is required for efficient CTL priming to HSV-1.

Neutrophils are prominent in epidermal and dermal layers of human herpetic lesions and are rapidly recruited into the skin follow epidermal abrasion and infection of mice with herpes simplex virus type-1 (HSV-1). Herein, we demonstrate that early production of neutrophil-attracting chemokines KC/MIP-2 is associated with transient recruitment of neutrophils into the skin of HSV-1-infected mice in temporal association with the development of herpetic lesions. Treatment of HSV-1-infected mice with a Ly6G-specific mAb induced systemic neutropenia, but surprisingly did not alter virus replication or lesion development. In contrast, depletion of Gr-1(+) cells with mAb RB6-8C5 led to enhanced virus growth and lesion severity. Thus, while neutrophils are prominent in zosteriform lesions of HSV-1-infected mice, they do not appear to play a major role in controlling virus replication or lesion development and/or healing. In contrast, Gr-1(+) cells limit both virus replication and lesion development in the zosteriform model.