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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
36
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pubmed:dateCreated |
2007-9-3
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pubmed:abstractText |
Mycobacterium tuberculosis lipomannans (LMs) modulate the host innate immune response. The total fraction of Mycobacterium bovis BCG LM was shown both to induce macrophage activation and pro-inflammatory cytokines through Toll-like receptor 2 (TLR2) and to inhibit pro-inflammatory cytokine production by lipopolysaccharide (LPS)-activated macrophages through a TLR2-independent pathway. The pro-inflammatory activity was attributed to tri- and tetra-acylated forms of BCG LM but not the mono- and di-acylated ones. Here, we further characterize the negative activities of M. bovis BCG LM on primary murine macrophage activation. We show that di-acylated LMs exhibit a potent inhibitory effect on cytokine and NO secretion by LPS-activated macrophages. The inhibitory activity of mycobacterial mannose-capped lipoarabino-mannans on human phagocytes was previously attributed to their binding to the C-type lectins mannose receptor or specific intracellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN). However, we found that di-acylated LM inhibition of LPS-induced tumor necrosis factor secretion by murine macrophages was independent of TLR2, mannose receptor, or the murine ortholog SIGNR1. We further determined that tri-acyl-LM, an agonist of TLR2/TLR1, promoted interleukin-12 p40 and NO secretion through the adaptor proteins MyD88 and TIRAP, whereas the fraction containing tetra-acylated LM activated macrophages in a MyD88-dependent fashion, mostly through TLR4. TLR4-dependent pro-inflammatory activity was also seen with M. tuberculosis LM, composed mostly of tri-acylated LM, suggesting that acylation degree per se might not be sufficient to determine TLR2 versus TLR4 usage. Therefore, LM acylation pattern determines the anti-inflammatory versus pro-inflammatory effects of LM through different pattern recognition receptors or signaling pathways and may represent an additional mean of regulating the host innate immunity by mycobacteria.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cell Adhesion Molecules,
http://linkedlifedata.com/resource/pubmed/chemical/DC-specific ICAM-3 grabbing...,
http://linkedlifedata.com/resource/pubmed/chemical/IL12B protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-12 Subunit p40,
http://linkedlifedata.com/resource/pubmed/chemical/Lectins, C-Type,
http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/MYD88 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Mannose-Binding Lectins,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Myd88 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Myeloid Differentiation Factor 88,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin-1,
http://linkedlifedata.com/resource/pubmed/chemical/TIRAP protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/TIRAP protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/TLR2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/TLR4 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Tlr2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Tlr4 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptor 1,
http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptor 2,
http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptor 4,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/lipoarabinomannan,
http://linkedlifedata.com/resource/pubmed/chemical/lipomannan,
http://linkedlifedata.com/resource/pubmed/chemical/mannose receptor
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
7
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pubmed:volume |
282
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
26014-25
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:17617634-Acylation,
pubmed-meshheading:17617634-Animals,
pubmed-meshheading:17617634-Cell Adhesion Molecules,
pubmed-meshheading:17617634-Cell Line,
pubmed-meshheading:17617634-Humans,
pubmed-meshheading:17617634-Immunity, Innate,
pubmed-meshheading:17617634-Inflammation,
pubmed-meshheading:17617634-Interleukin-12 Subunit p40,
pubmed-meshheading:17617634-Lectins, C-Type,
pubmed-meshheading:17617634-Lipopolysaccharides,
pubmed-meshheading:17617634-Macrophage Activation,
pubmed-meshheading:17617634-Macrophages,
pubmed-meshheading:17617634-Mannose-Binding Lectins,
pubmed-meshheading:17617634-Membrane Glycoproteins,
pubmed-meshheading:17617634-Mice,
pubmed-meshheading:17617634-Mice, Knockout,
pubmed-meshheading:17617634-Mycobacterium bovis,
pubmed-meshheading:17617634-Mycobacterium tuberculosis,
pubmed-meshheading:17617634-Myeloid Differentiation Factor 88,
pubmed-meshheading:17617634-Nitric Oxide,
pubmed-meshheading:17617634-Receptors, Cell Surface,
pubmed-meshheading:17617634-Receptors, Interleukin-1,
pubmed-meshheading:17617634-Signal Transduction,
pubmed-meshheading:17617634-Toll-Like Receptor 1,
pubmed-meshheading:17617634-Toll-Like Receptor 2,
pubmed-meshheading:17617634-Toll-Like Receptor 4,
pubmed-meshheading:17617634-Tumor Necrosis Factor-alpha
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pubmed:year |
2007
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pubmed:articleTitle |
Acylation determines the toll-like receptor (TLR)-dependent positive versus TLR2-, mannose receptor-, and SIGNR1-independent negative regulation of pro-inflammatory cytokines by mycobacterial lipomannan.
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pubmed:affiliation |
Orleans University and CNRS, Molecular Immunology and Embryology, UMR6218, 45071 Orléans, France.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
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