Please use this identifier to cite or link to this item: http://localhost:8080/xmlui/handle/123456789/1031
Title: Lipoglycans contribute to innate immune detection of mycobacteria
Authors: Shyam Krishna
Ray, A
Dubey, S K
Larrouy-Maumus, G
Chalut, C
Castanier, R
Noguera, A
Gilleron, M
Puzo, G
Vercellone, A
Nampoothiri, K M
Nigou, J
Keywords: Lipoarabinomannan
TLR2
Lipoproteins
Tuberculosis
Staphylococcus-aureus
Lipoteichoic acid
Toll-like receptors
Issue Date: 2011
Publisher: Public Library Science
Citation: PLoS ONE 6(12):Article No.28476;02 Dec 2011
Abstract: Innate immune recognition is based on the detection, by pattern recognition receptors (PRRs), of molecular structures that are unique to microorganisms. Lipoglycans are macromolecules specific to the cell envelope of mycobacteria and related genera. They have been described to be ligands, as purified molecules, of several PRRs, including the C-type lectins Mannose Receptor and DC-SIGN, as well as TLR2. However, whether they are really sensed by these receptors in the context of a bacterium infection remains unclear. To address this question, we used the model organism Mycobacterium smegmatis to generate mutants altered for the production of lipoglycans. Since their biosynthesis cannot be fully abrogated, we manipulated the biosynthesis pathway of GDP-Mannose to obtain some strains with either augmented (similar to 1.7 fold) or reduced (similar to 2 fold) production of lipoglycans. Interestingly, infection experiments demonstrated a direct correlation between the amount of lipoglycans in the bacterial cell envelope on one hand and the magnitude of innate immune signaling in TLR2 reporter cells, monocyte/macrophage THP-1 cell line and human dendritic cells, as revealed by NF-kappa B activation and IL-8 production, on the other hand. These data establish that lipoglycans are bona fide Microbe-Associated Molecular Patterns contributing to innate immune detection of mycobacteria, via TLR2 among other PRRs.
URI: http://ir.niist.res.in:8080/jspui/handle/123456789/1031
ISSN: 1932-6203
Appears in Collections:2011

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