Individual plasmacytoid dendritic cells are major contributors to the production of multiple innate cytokines in an organ-specific manner during viral infection

Nicolas Zucchini, Gilles Bessou, Scott H. Robbins, Lionel Chasson, Anna Raper, Paul R. Crocker, Marc Dalod

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    Abstract

    Plasmacytoid dendritic cells (pDCs) are an important source of IFN-alpha/beta in response to a variety of viruses in vivo, including murine cytomegalovirus (MCMV). However, the respective contributions of various infected organs, and within these of pDCs, conventional dendritic cells and other cells, to the systemic production of IFN-alpha/beta or other innate cytokines during viral infections in vivo is largely unknown. Whether a specialization of pDC subsets in the production of different patterns of innate cytokines exists in vivo in response to a viral infection has not been investigated. Here, by analyzing for the first time directly ex vivo, at the single-cell level, the simultaneous production of up to three cytokines in pDCs isolated from MCMV-infected mice, we show that (i) pDCs are the quasi-exclusive source of IFN-alpha/beta, IL-12 and tumor necrosis factor (TNF)-alpha, early during MCMV infection, in two immunocompetent mouse lines and with two viral strains, (ii) pDC activation for IFN-alpha/beta production is organ specific and (iii) a significant proportion of pDCs simultaneously produce IFN-alpha/beta, TNF-alpha and IL-12, although TNF-alpha and IFN-alpha/beta appear more often co-expressed with one another than each of them with IL-12. Altogether, these results show a broad and non-redundant role of pDCs in early innate detection of, and defense against, viral infection. The data also show differences in the responsiveness of pDCs from different tissues and suggest distinct molecular requirements for pDC production of various cytokines. These observations must be taken into account when designing new antiviral vaccination strategies aimed at harnessing pDC responses.

    Original languageEnglish
    Pages (from-to)45-56
    Number of pages12
    JournalInternational Immunology
    Volume20
    Issue number1
    DOIs
    Publication statusPublished - Jan 2008

    Keywords

    • Dendritic cells
    • IFN-alpha/beta
    • IL-12
    • Murine cytomegalovirus
    • Tumor necrosis factor-alpha
    • Murine cytomegalovirus infection
    • Respiratory syncytial virus
    • IIFN-producing cells
    • Interferon alpha/beta
    • Immune responses
    • Bone marrow
    • Siglec-H
    • In vivo
    • Mouse
    • Activation

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