Abstract
(English)
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Inhibition of dendritic cell maturation by herpes simplex virus
Mariolina Salio1, Marina Cella1, Mark Suter2 and Antonio Lanzavecchia1
1 Basel Institute for Immunology, Grenzacherstrasse 487, CH 4005, Basel,
Switzerland.
2 Institute of Virology, University of Zurich, Winterthurerstrasse 266a,
CH-8057 Zürich, Switzerland.
As potent antigent presenting cells, dendritic cells (DC) play an important role in initiating immune responses. In their immature form, DC reside in peripheral tissues, where they exert their sentinel role for incoming pathogens. Maturation of DC, leading to migration and increased T cell stimulatory capacity, is essential for the initiation of imm
une responses. This process is triggered by a variety of stimuli, such as inflammatory cytokines, bacterial and viral products. We have been studying interaction of DC with Herpes simplex viruses. Using a recombinant disabled infectious single cycle (DISC) herpes simplex virus 1 (HSV-1) encoding green fluorescent protein (GFP), we show that the infected DC fail to upregulate costimulatory molecules, produce cytokines, and do not acquire responsiveness to chemokines required for migration to secondary lymphoid organs. The inhibition of DC maturation by HSV is a dominant effect and cannot be rescued by additional maturation stimuli, such as LPS or TNFa. These results reveal yet another strategy used by HSV-1 to evade the immune response, namely the inhibition of signaling pathways involved in DC maturation. We are currently investigating the molecular mechanism of this inhibition.
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