Role for plasmacytoid dendritic cells in the immune control of recurrent human herpes simplex virus infection.
Plasmacytoid dendritic cells (pDC) are an important component of the innate immune response, producing large amounts of alpha interferon in response to viral stimulation in vitro. Under noninflammatory conditions, pDC are not found in the skin and are restricted in location to the blood and lymph nodes. Therefore, their role in mucosal and cutaneous herpes simplex virus (HSV) infection has not been well-defined. In this study we show a role for human pDC in the immune response to HSV infection. First, by confocal microscopy we showed that pDC infiltrate the dermis of recurrent genital herpes simplex lesions at early and late phases, often at the dermo-epidermal junction. We then showed that pDC in vitro are resistant to HSV infection despite expressing the entry receptors CD111, CD112, and HVE-A. Within the lesions, pDC were found closely associated with CD3(+) lymphocytes and NK cells, especially those which were activated (CD69(+)). Furthermore, these HSV-exposed pDC were able to stimulate virus-specific autologous T-lymphocyte proliferation. We conclude from this work that pDC may contribute to the immune control of recurrent herpes virus infection in vivo.
Donaghy
Heather
H
Centre for Virus Research, Westmead Millennium Institute, Sydney, Australia.
Bosnjak
Lidija
L
Harman
Andrew N
AN
Marsden
Valerie
V
Tyring
Stephen K
SK
Meng
Tze-Chiang
TC
Cunningham
Anthony L
AL
D015815:Cell Adhesion Molecules / Q000032:analysis; D003713:Dendritic Cells / Q000737:chemistry / Q000276:immunology* / Q000821:virology; D020405:Dermis / Q000276:immunology; D006558:Herpes Genitalis / Q000276:immunology* / Q000473:pathology; D006801:Humans; D053646:Interleukin-2 Receptor beta Subunit / Q000032:analysis; D007694:Killer Cells, Natural / Q000276:immunology; D016131:Lymphocyte Subsets / Q000276:immunology; D000075983:Nectins; D053240:Receptors, Tumor Necrosis Factor, Member 14 / Q000032:analysis; D011991:Receptors, Virus / Q000032:analysis; D018139:Simplexvirus / Q000276:immunology*
D015815:Cell Adhesion Molecules; C508020:IL2RB protein, human; D053646:Interleukin-2 Receptor beta Subunit; C000619010:NECTIN1 protein, human; D000075983:Nectins; D053240:Receptors, Tumor Necrosis Factor, Member 14; D011991:Receptors, Virus