Impact of Varicella-Zoster Virus on Dendritic Cell Subsets in Human Skin during Natural Infection

University of Sydney, Discipline of Infectious Diseases and Immunology, Blackburn Building, Room 601, New South Wales 2006, Australia.
Journal of Virology (Impact Factor: 4.44). 04/2010; 84(8):4060-72. DOI: 10.1128/JVI.01450-09
Source: PubMed


Varicella-zoster virus (VZV) causes varicella and herpes zoster, diseases characterized by distinct cutaneous rashes. Dendritic cells (DC) are essential for inducing antiviral immune responses; however, the contribution of DC subsets to immune control during natural cutaneous VZV infection has not been investigated. Immunostaining showed that compared to normal skin, the proportion of cells expressing DC-SIGN (a dermal DC marker) or DC-LAMP and CD83 (mature DC markers) were not significantly altered in infected skin. In contrast, the frequency of Langerhans cells was significantly decreased in VZV-infected skin, whereas there was an influx of plasmacytoid DC, a potent secretor of type I interferon (IFN). Langerhans cells and plasmacytoid DC in infected skin were closely associated with VZV antigen-positive cells, and some Langerhans cells and plasmacytoid DC were VZV antigen positive. To extend these in vivo observations, both plasmacytoid DC (PDC) isolated from human blood and Langerhans cells derived from MUTZ-3 cells were shown to be permissive to VZV infection. In VZV-infected PDC cultures, significant induction of alpha IFN (IFN-alpha) did not occur, indicating the VZV inhibits the capacity of PDC to induce expression of this host defense cytokine. This study defines changes in the response of DC which occur during cutaneous VZV infection and implicates infection of DC subtypes in VZV pathogenesis.

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Available from: Najla Nasr, Oct 05, 2015
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    • "DC resident in the skin are almost exclusively of the myeloid lineage. Recently, a distinctly different subset, plasmacytoid dendritic cells (pDC), normally absent in skin, were shown to migrate to inflamed skin lesions of autoimmune reactions such as psoriasis (Albanesi et al., 2010; Nestle et al., 2005) and lupus erythematosus (Farkas et al., 2001; Meller et al., 2005), as well as to virally induced lesions of herpes simplex (Donaghy et al., 2009; Peng et al., 2009) and varicella (Gerlini et al., 2006; Huch et al., 2010). pDC are thought to play a central role in the response to viruses through their capacity to produce high amounts of IFNα, which is primarily induced by microbial nucleic acids signalling via Toll-Like Receptor (TLR) 7 and 9 (Gilliet et al., 2008). "
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    ABSTRACT: Plasmacytoid dendritic cells (pDCs) are rarely present in normal skin but have been shown to infiltrate lesions of infections or autoimmune disorders. Here, we report that several DC subsets including CD123(+) BDCA-2/CD303(+) pDCs accumulate in the dermis in indurations induced by the tuberculin skin test (TST), used to screen immune sensitization by Mycobacterium tuberculosis. Although the purified protein derivate (PPD) used in the TST did not itself induce pDC recruitment or IFN-α production, the positive skin reactions showed high expression of the IFN-α-inducible protein MxA. In contrast, the local immune response to PPD was associated with substantial cell death and high expression of the cationic antimicrobial peptide LL37, which together can provide a means for pDC activation and IFN-α production. In vitro, pDCs showed low uptake of PPD compared with CD11c(+) and BDCA-3/CD141(+) myeloid DC subsets. Furthermore, supernatants from pDCs activated with LL37-DNA complexes reduced the high PPD uptake in myeloid DCs, as well as decreased their capacity to activate T-cell proliferation. Infiltrating pDCs in the TST reaction site may thus have a regulatory effect upon the antigen processing and presentation functions of surrounding potent myeloid DC subsets to limit potentially detrimental and excessive immune stimulation.
    Journal of Investigative Dermatology 08/2011; 132(1):114-23. DOI:10.1038/jid.2011.246 · 7.22 Impact Factor
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