A Simple Glycolipid Mimic of the Phosphatidylinositol Mannoside Core from Mycobacterium tuberculosis Inhibits Macrophage Cytokine Production
Author(s)
Mosaiab, Tamim
Boiteux, Sandra
Zulfiker, Abu Hasanat Md
Wei, Ming Q
Kiefel, Milton J
Houston, Todd A
Year published
2018
Metadata
Show full item recordAbstract
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 ...
View more >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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View more >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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Journal Title
ChemBioChem
Volume
19
Issue
4
Subject
Medicinal and biomolecular chemistry
Biochemistry and cell biology
Biochemistry and cell biology not elsewhere classified
Inflammation
Lectins
Macrophages
Mincle
Mannose