Impact of varicella-zoster virus on dendritic cell subsets in human skin during natural infection.
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.
University of Sydney, Discipline of Infectious Diseases and Immunology, Blackburn Building, Room 601, New South Wales 2006, Australia.
Jennifer H
JH
Huch
Anthony L
AL
Cunningham
Ann M
AM
Arvin
Najla
N
Nasr
Saskia J A M
SJ
Santegoets
Eric
E
Slobedman
Barry
B
Slobedman
Allison
A
Abendroth
D015703:Antigens, CD / Q000032:analysis; D015815:Cell Adhesion Molecules / Q000032:analysis; D002478:Cells, Cultured; D002644:Chickenpox / Q000276:immunology* / Q000473:pathology; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology; D005434:Flow Cytometry; D006562:Herpes Zoster / Q000276:immunology* / Q000473:pathology; D014645:Herpesvirus 3, Human / Q000276:immunology*; D006801:Humans; D007136:Immunoglobulins / Q000032:analysis; D007150:Immunohistochemistry; D016898:Interferon-alpha / Q000378:metabolism; D037181:Lectins, C-Type / Q000032:analysis; D051907:Lysosomal Membrane Proteins / Q000032:analysis; D008562:Membrane Glycoproteins / Q000032:analysis; D008853:Microscopy; D011956:Receptors, Cell Surface / Q000032:analysis; D012867:Skin / Q000276:immunology* / Q000473:pathology; D000097802:CD83 Antigen; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D016898:Interferon-alpha; D037181:Lectins, C-Type; D051907:Lysosomal Membrane Proteins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D000097802:CD83 Antigen; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin