Regulation of macrophage IL-12 synthesis by Leishmania phosphoglycans

Piedrafita, D. et al. (1999) Regulation of macrophage IL-12 synthesis by Leishmania phosphoglycans. European Journal of Immunology, 29(1), pp. 235-244. (doi: 10.1002/(SICI)1521-4141(199901)29:01<235::AID-IMMU235>3.0.CO;2-S) (PMID:9933105)

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Abstract

It is now generally accepted that IFN-γ, 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 parasites 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(β1-4)mannose(α1)-PO4 repeating units and not the glycophosphoinositol lipid anchor of lipophosphoglycan. At the concentration used, sPG had no effect on the release of TNF-α or IL-6 in activated macrophages. The inhibition of IL-12(p40) production was at the transcriptional level, but was not mediated through NFκB inhibition. These data demonstrate that PG may be an important molecule for the establishment and survival of the parasite in permissive hosts.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Liew, Professor Foo and Sands, Dr William and Xu, Dr Damo and Brewer, Professor James
Authors: Piedrafita, D., Proudfoot, L., Nikolaev, A. V., Xu, D., Sands, W., Feng, G.-J., Thomas, E., Brewer, J., Ferguson, M. A.J., Alexander, J., and Liew, F.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:European Journal of Immunology
Publisher:Wiley
ISSN:0014-2980
ISSN (Online):1521-4141

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