title: Relay of herpes simplex virus between Langerhans cells and dermal dendritic cells in human skin.
abstract: The mechanism by which immunity to Herpes Simplex Virus (HSV) is initiated is not completely defined. HSV initially infects mucosal epidermis prior to entering nerve endings. In mice, epidermal Langerhans cells (LCs) are the first dendritic cells (DCs) to encounter HSV, but it is CD103(+) dermal DCs that carry viral antigen to lymph nodes for antigen presentation, suggesting DC cross-talk in skin. In this study, we compared topically HSV-1 infected human foreskin explants with biopsies of initial human genital herpes lesions to show LCs are initially infected then emigrate into the dermis. Here, LCs bearing markers of maturation and apoptosis formed large cell clusters with BDCA3(+) dermal DCs (thought to be equivalent to murine CD103(+) dermal DCs) and DC-SIGN(+) DCs/macrophages. HSV-expressing LC fragments were observed inside the dermal DCs/macrophages and the BDCA3(+) dermal DCs had up-regulated a damaged cell uptake receptor CLEC9A. No other infected epidermal cells interacted with dermal DCs. Correspondingly, LCs isolated from human skin and infected with HSV-1 in vitro also underwent apoptosis and were taken up by similarly isolated BDCA3(+) dermal DCs and DC-SIGN(+) cells. Thus, we conclude a viral antigen relay takes place where HSV infected LCs undergo apoptosis and are taken up by dermal DCs for subsequent antigen presentation. This provides a rationale for targeting these cells with mucosal or perhaps intradermal HSV immunization.
authors: Centre for Virus Research, Westmead Millennium Institute, Sydney, Australia; Sydney Medical School, University of Sydney, Sydney, Australia.
authors: Min
authors: M
authors: Kim
authors: Centre for Virus Research, Westmead Millennium Institute, Sydney, Australia; Sydney Medical School, University of Sydney, Sydney, Australia.
authors: Naomi R
authors: NR
authors: Truong
authors: Centre for Virus Research, Westmead Millennium Institute, Sydney, Australia.
authors: Virginia
authors: V
authors: James
authors: Centre for Virus Research, Westmead Millennium Institute, Sydney, Australia.
authors: Lidija
authors: L
authors: Bosnjak
authors: Centre for Virus Research, Westmead Millennium Institute, Sydney, Australia; Sydney Medical School, University of Sydney, Sydney, Australia.
authors: Kerrie J
authors: KJ
authors: Sandgren
authors: Centre for Virus Research, Westmead Millennium Institute, Sydney, Australia; Sydney Medical School, University of Sydney, Sydney, Australia.
authors: Andrew N
authors: AN
authors: Harman
authors: Centre for Virus Research, Westmead Millennium Institute, Sydney, Australia; Sydney Medical School, University of Sydney, Sydney, Australia.
authors: Najla
authors: N
authors: Nasr
authors: Centre for Virus Research, Westmead Millennium Institute, Sydney, Australia; Sydney Medical School, University of Sydney, Sydney, Australia.
authors: Kirstie M
authors: KM
authors: Bertram
authors: Sydney Institute of Plastic and Reconstructive Surgery, Sydney, Australia.
authors: Norman
authors: N
authors: Olbourne
authors: Sydney Medical School, University of Sydney, Sydney, Australia; Western Sydney Sexual Health Centre, Sydney, Australia.
authors: Shailandra
authors: S
authors: Sawleshwarkar
authors: Western Sydney Sexual Health Centre, Sydney, Australia.
authors: Kaylene
authors: K
authors: McKinnon
authors: Department of Surgery, Children's Hospital at Westmead, Sydney, Australia.
authors: Ralph C
authors: RC
authors: Cohen
authors: Centre for Virus Research, Westmead Millennium Institute, Sydney, Australia; Sydney Medical School, University of Sydney, Sydney, Australia.
authors: Anthony L
authors: AL
authors: Cunningham
mesh_terms: D002465:Cell Movement; D003713:Dendritic Cells / Q000821:virology*; D005434:Flow Cytometry; D018259:Herpesvirus 1, Human / Q000502:physiology*; D006801:Humans; D007801:Langerhans Cells / Q000821:virology*; D008856:Microscopy, Fluorescence; D018139:Simplexvirus / Q000472:pathogenicity*; D012867:Skin / Q000821:virology*