A Simple Glycolipid Mimic of the Phosphatidylinositol Mannoside Core from Mycobacterium tuberculosis Inhibits Macrophage Cytokine Production |
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| Authors: | Tamim Mosaiab Sandra Boiteux Dr Abu Hasanat Md Zulfiker Dr Ming Q Wei Dr Milton J Kiefel Dr Todd A Houston |
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| Affiliation: | 1. Institute for Glycomics, Griffith University, Southport, Queensland, Australia;2. Menzies Health Institute Queensland and School of Medical Science, Griffith University, Southport, Queensland, Australia;3. Department of Biomedical Sciences, John C. Edwards School of Medicine, Marshall University, Huntington, WV, USA |
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| Abstract: | Glycolipids from Mycobacterium tuberculosis have a profound impact on the innate immune response of the host. Macrophage‐inducible C‐type lectin (Mincle) is a pattern‐recognition receptor that has been shown to bind trehalose dimycolate (TDM) from the mycobacterium and instigate intracellular signalling in the immune cell. There are structural similarities between the structures of TDM and phosphatidyl inositol mannoside (PIM). We thus hypothesized that these latter structures might also modulate an immune response in a similar manner. To test this, we synthesized a series of new mannose derivatives modified with fatty esters at the 6‐position and assessed the release of inflammatory cytokines in human U937 macrophages under the induction of lipopolysaccharides (LPS) after glycolipid treatment. The results showed that the amount of two major cytokines—tumour necrosis factor (TNF)‐α and interleukin (IL)‐6—released from LPS‐stimulated U937 cells decreased significantly when compared to a control upon treatment with the prepared glycolipids, thus indicating a reduction in cytokine production by the macrophages. |
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| Keywords: | inflammation lectins macrophages mannose Mincle |
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