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O06.2 Initial interactions of herpes simplex virus with human skin dendritic cells
  1. Cunningham AL1,
  2. M Kim1,
  3. Truong NR1,
  4. Sandgren KJ1,
  5. Harman AN1,
  6. Bertram KM1,
  7. L Bosnjak2,
  8. N Nasr1,
  9. N Olbourne3,
  10. S Sawleshwarkar4,
  11. V James2,
  12. K Mckinnon5,
  13. Cohen RC6
  1. 1The Westmead Institute For Medical Research And University of Sydney, Westmead, Australia
  2. 2The Westmead Institute for Medical Research, Westmead, Australia
  3. 3Sydney Institute of Plastic and Reconstructive Surgery, Sydney, Australia
  4. 4Western Sydney Sexual Health Centre, Parramatta, Australia
  5. 5Western Sydney Sexual Health Centre, Westmead, Australia
  6. 6Children’s Hospital At Westmead, Westmead, Australia

Abstract

Introduction HSV2 initially infects the stratified squamous epithelium of the anogenital mucosa prior to entering nerve endings, resulting in lifelong latent infection of neurons in the dorsal root ganglia. We have recently reported that topical application of HSV-1 to the inner surface of human foreskin explants, simulating in vivo infection, infects epidermal Langerhans cells (LCs) which then emigrate into the dermis. Here they formed large cell clusters with dermal dendritic cells (DCs). HSV-expressing LC fragments were observed inside the dermal DCs/macrophages.

Methods To define the mechanism of this interaction, we isolated LCs and dermal DCs from large human abdominal skin specimens by flow sorting. LCs were infected with HSV2 and co-cultured with dermal DCs.

Results All infected LCs developed apoptosis and fragments of them were observed within the dermal DC cytoplasm. HSV infected LCs expressed several chemokines as RNA and protein, with corresponding receptors expressed on dermal DC subsets. These DCs also expressed several phagocytic/apoptotic receptors for phosphatidylserine. In genital herpes lesions the selective contact of CD8 T cells with one of three dermal DC subsets was observed. The distribution of CD4 T cells and contact with these DC subsets is eventually being studied.

Conclusion Thus, we conclude that a viral antigen relay takes place whereby HSV infected LCs undergo apoptosis and are taken up by dermal DCs by phagocytosis for subsequent antigen presentation, probably via different pathways for CD4 and CD8 T cells. As dendritic cells are key targets for the new generation of vaccine adjuvants these studies define potential cellular targets for mucosal vaccines.

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