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Migration of plasmacytoid dendritic cells into herpes simplex type 2 lesions: implications for transmission of HIV
Presented by Heather Donaghy, Australia.
Donaghy H.1, Bosnjak L.1, Harman A.1, Marsden V.1, Cunningham A.L.2
1Westmead Millennium Institute, Centre for Virus Research, Westmead NSW, Australia, 2Westmead Millennium Institute and University of Sydney, Westmead NSW, Australia
Objectives: Plasmacytoid dendritic cells (pDCs) produce interferon alpha (IFNa) in response to stimulation with viruses especially herpes simplex virus (HSV). HIV infects pDCs and co-infects herpes lesions. However, little is known about the role of pDCs in human HSV infections. In this study we investigated whether pDCs were located at sites of HSV infection such as the skin and the role that these cells may play in mucosal immunity to HSV and ultimately in HIV co-infection.
Methods: Biopsies were taken from patients with herpes simplex lesions and BDCA-2+ pDCs were identified by confocal microscopy. Isolated blood pDCs were exposed to live HSV-2 (186) for 1 hour and cultured for 16-24 hours in the presence of IL-3. After culture pDCs were assessed for viability, co-stimulatory molecule expression and IFNa production. Productive infection was determined by cell surface expression of viral protein gC using flow cytometry as well as by quantitative PCR for 6 HSV genes in direct comparison with autologous MDDCs.
Results: Infiltration of pDCs into the dermis of herpes simplex infected lesions was demonstrated. In vitro infection of blood pDCs with HSV-2 showed that pDCs are not infected with HSV but do undergo maturation, produce IFNa and are able to stimulate autologous T lymphocyte proliferation. IFNa production is not responsible for the refractoriness to infection.
Conclusions: The location of pDCs in the dermis of herpes simplex lesion biopsies suggests a role for these cells in the control of virus dissemination at mucosal surfaces. That these cells respond to HSV stimulation by production of IFNa without infection suggests a protective role of pDCs in HSV infection. As pDCs are productively infected with HIV, their infiltration into the skin during recurrent herpes lesions may provide an additional entry mechanism for HIV, contributing to the increased susceptibility of HSV infected individuals to HIV.
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