Regulation of macrophage IL-12 synthesis by Leishmania phosphoglycans

David Piedrafita, Lorna Proudfoot, Andrei V. Nikolaev, Damo Xu, William Sands, Gui-Jie Feng, Elaine Thomas, James Brewer, Michael A. J. Ferguson, James Alexander, Foo Y. Liew

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    47 Citations (Scopus)

    Abstract

    It is now generally accepted that IFN-gamma, secreted by Th1 cells, is the most potent cytokine leading to macrophage activation and host resistance against infection with the intracellular protozoan parasite Leishmania. It is also established that IL-12 is a critical cytokine involved in the differentiation and expansion of Th1 cells. Therefore, the ability of Leishmania para sites to actively suppress IL-12 production by host macrophages may be an important strategy for parasite survival. Here we report that a major parasite cell surface molecule, phosphoglycan (PG), of Leishmania could selectively inhibit the synthesis of IL-12(p40, p70) by activated murine macrophages. Furthermore, synthetic PG (sPG) was able to inhibit IL-12 release in a dose-dependent manner. Inhibition was dependent on the galactose(beta 1-4)mannose(alpha 1)-PO4 repeating units and not the glycophosphoinositol lipid anchor of lipo-phosphoglycan. Al the concentration used, sPG had no effect on the release of TNF-alpha or IL-6 in activated macrophages. The inhibition of IL-12(p40) production was at the transcriptional level, but was not mediated through NF kappa B inhibition. These data demonstrate that PG may be an important molecule for the establishment and survival of the parasite in permissive hosts.

    Original languageEnglish
    Pages (from-to)235-244
    Number of pages10
    JournalEuropean Journal of Immunology
    Volume29
    Issue number1
    DOIs
    Publication statusPublished - Jan 1999

    Keywords

    • Leishmania
    • IL-12
    • Phosphoglycan
    • Regulation

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