Epstein-Barr Virus Promotes Interferon-a Production by Plasmacytoid Dendritic Cells

Objective Epstein-Barr virus (EBV) infection has been linked to systemic lupus erythematosus (SLE), as demonstrated by the presence of increased seroprevalence and elevated viral loads, but the mechanism of this linkage has not been elucidated. Increased interferon- (IFN) levels and signatures, whic...

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Bibliographic Details
Published in:Arthritis and rheumatism 2010-06, Vol.62 (6), p.1693-1701
Main Authors: QUAN, Timothy E, ROMAN, Robert M, RUDENGA, Benjamin J, HOLERS, V. Michael, CRAFT, Joseph E
Format: Article
Language:English
Subjects:
Biological and medical sciences
Diseases of the osteoarticular system
Epstein-Barr virus
Medical sciences
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Summary:Objective Epstein-Barr virus (EBV) infection has been linked to systemic lupus erythematosus (SLE), as demonstrated by the presence of increased seroprevalence and elevated viral loads, but the mechanism of this linkage has not been elucidated. Increased interferon- (IFN) levels and signatures, which are associated with innate immune responses, have been found in patients with SLE. Plasmacytoid dendritic cells (PDCs) are innate immune cells that mediate viral immunity by producing large quantities of IFN, but the role they play during infection with EBV remains unclear. To address this issue, we investigated the ability of EBV to promote IFN production by PDCs in healthy subjects. Methods Human PDCs were sorted and cultured in the presence of EBV, EBV-encoded RNA, and EBV double-stranded DNA. IFN production by PDCs was measured by enzyme-linked immunosorbent assay, with the activation of these cells measured by flow cytometry. Results We found that EBV DNA and RNA promoted IFN production by human PDCs through engagement of Toll-like receptor 9 (TLR-9) and TLR-7, respectively, with the initial viral recognition by PDCs mediated by binding to class II major histocompatibility complex (MHC) molecules. Conclusion These data demonstrate that class II MHC-specific engagement by virus, with subsequent viral nucleic acid recognition, mediates IFN production by PDCs. Our results suggest that elevated levels of IFN found in SLE patients may be a result of aberrantly controlled chronic viral infection.
ISSN:0004-3591
1529-0131
DOI:10.1002/art.27408