Journal article
Identification of an important immunological difference between virulent varicella-zoster virus and its avirulent vaccine: viral disruption of dendritic cell instruction
The Journal of immunology (1950), Vol.185(1), pp.488-497
07/01/2010
DOI: 10.4049/jimmunol.0902817
PMCID: PMC3033232
PMID: 20525895
Abstract
Virulent Varicella-zoster virus (VZV) can spread in immunocompetent humans, resulting in symptoms mostly of the skin. In contrast, vaccine Oka (V-Oka), the attenuated VZV vaccine strain, only rarely causes clinical reactions. The mechanisms underlying these pathogenetic differences are unclear. In this study, we comparatively analyzed the ability of virulent VZV and V-Oka to modulate instruction of dendritic cells (DCs) by innate signals. DCs isolated from normal human skin were susceptible to infection with both VZV and V-Oka. Moreover, inflammatory DCs, which play a crucial role in stimulation of T helper type 1 (Th1) immune responses, accumulated in herpes zoster lesions. Infection of inflammatory DCs generated
in vitro
with either virulent VZV or V-Oka resulted in upregulation of CD1c. Upon coculture with CD1c-restricted innate cells, DCs developed a mature phenotype whether infected with virulent VZV or V-Oka. Intriguingly, a striking difference was detected on the functional level. The release of IFN-γ and IL-12, the signature cytokines of Th1 responses, was enhanced by V-Oka but blocked by virulent VZV. V-Oka and virulent VZV efficiently synergized with CD40L, eliminating the possibility that CD40 signaling was a target of VZV-associated immune evasion. Instead, virulent VZV selectively interfered with signaling through TLR2, which is known to sense VZV. Thus, virulent VZV subverts Th1-promoting instruction of human DCs by blocking TLR2-mediated innate signals that prime IL-12 production by DCs. Taken together, our results demonstrate a novel immune evasion mechanism of virulent VZV that has been lost during the attenuation process leading to the VZV vaccine strain.
Details
- Title: Subtitle
- Identification of an important immunological difference between virulent varicella-zoster virus and its avirulent vaccine: viral disruption of dendritic cell instruction
- Creators
- Cindy Gutzeit - Institute of Virology, Charité – Universitätsmedizin Berlin, Berlin, GermanyMartin J Raftery - Institute of Virology, Charité – Universitätsmedizin Berlin, Berlin, GermanyMatthias Peiser - Institute of Molecular Biology and Bioinformatics, Charité – Universitätsmedizin Berlin, Berlin, GermanyKarsten B Tischer - Institute of Virology, Department of Veterinary Medicine, Freie Universität Berlin, Berlin, GermanyMartina Ulrich - Department of Dermatology, Venerology and Allergology, Charité – Universitätsmedizin Berlin, Berlin, GermanyMelanie Eberhardt - Institute of Virology, Charité – Universitätsmedizin Berlin, Berlin, GermanyEggert Stockfleth - Department of Dermatology, Venerology and Allergology, Charité – Universitätsmedizin Berlin, Berlin, GermanyThomas Giese - Institute of Immunology, University of Heidelberg, Heidelberg, GermanyAndreas Sauerbrei - Institute of Virology and Antiviral Therapy, Friedrich-Schiller University of Jena, Jena, GermanyCraig T Morita - Division of Rheumatology, Department of Internal Medicine and the Interdisciplinary Graduate Program in Immunology, University of Iowa College of Medicine, Iowa City, IA 52242, USAGünther Schönrich - Institute of Virology, Charité – Universitätsmedizin Berlin, Berlin, Germany
- Resource Type
- Journal article
- Publication Details
- The Journal of immunology (1950), Vol.185(1), pp.488-497
- DOI
- 10.4049/jimmunol.0902817
- PMID
- 20525895
- PMCID
- PMC3033232
- NLM abbreviation
- J Immunol
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Language
- English
- Date published
- 07/01/2010
- Academic Unit
- Immunology; Internal Medicine
- Record Identifier
- 9984094740302771
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