A Lipomannan Variant with Strong TLR-2-dependent Pro-inflammatory Activity in Saccharothrix aerocolonigenes

Gibson, Kevin J.; Gilleron, Martine; Constant, Patricia; Sichi, Bénédicte; Puzo, Germain; Besra, Gurdyal S.; Nigou, Jérôme

doi:10.1074/jbc.m505498200

Cited by 25 publications

(23 citation statements)

References 52 publications

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“…These cells express at their surface high levels of TLR2 but barely detectable levels of TLR4 (not shown) (41). We previously established, using blocking Abs, that the cytokine release induced by the various lipoglycans studied here was dependent on TLR2 but not TLR4 (15,16). Each lipoglycan was tested at concentrations of 10 and 20 g/ml (Fig.…”

Section: Activation Of Thp-1 Cellsmentioning

confidence: 71%

“…2). Indeed, SaeLM, BCGLM, and TpaLM, the most active molecules, have mannan domains built from 36, 25, and 11 Manp units on average, respectively, and differ by the side chains substituting the (␣136)-Manp backbone, which are dimannosyl units, monomannosyl units, or no units, respectively (15,16,20) (Fig. 1, Table I).…”

Section: Activation Of Thp-1 Cellsmentioning

confidence: 99%

“…The mannan domain of SaeLM is larger when compared with that of BCGLM. However, this mainly results from longer side chains for the former (i.e., dimannosyl vs single mannosyl units) (15) (Fig. 1, Table I).…”

Section: Activation Of Hek-tlr2 Cellsmentioning

confidence: 99%

“…However, in most cases, they are simpler in structure. Most particularly, the arabinan moiety of the molecule can be reduced to single arabinosyl susbtituents (15,16,(25)(26)(27) (Fig. 1).…”

mentioning

confidence: 99%

“…1). These different lipoglycan variants, either LAM or LM, show variable TLR2-dependent proinflammatory activities (15,16).…”

mentioning

confidence: 99%

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Mannan Chain Length Controls Lipoglycans Signaling via and Binding to TLR2

Nigou¹,

Vasselon²,

Ray³

et al. 2008

The Journal of Immunology

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TLR2 is a pattern-recognition receptor that is activated by a large variety of conserved microbial components, including lipoproteins, lipoteichoic acids, and peptidoglycan. Lipoglycans are TLR2 agonists found in some genera of the phylogenetic order Actinomycetales, including Mycobacterium. They are built from a mannosyl-phosphatidyl-myo-inositol anchor attached to a (alpha1-->6)-linked d-mannopyranosyl chain whose units can be substituted by d-mannopyranosyl and/or d-arabinofuranosyl units. At this time, little is known about the molecular bases underlying their ability to induce signaling via this receptor. We have recently shown that the anchor must be at least triacylated, including a diacylglyceryl moiety, whereas the contribution of the glycosidic moiety is not yet clearly defined. We show herein that lipoglycan activity is directly determined by mannan chain length. Indeed, activity increases with the number of units constituting the (alpha1-->6)-mannopyranosyl backbone but is also critically dependent on the substitution type of the 2-hydroxyl of these units. We thus provide evidence for the definition of a new pattern that includes the nonlipidic moiety of the molecules, most probably as a result of the (alpha1-->6)-mannopyranosyl backbone being a highly conserved structural feature among lipoglycans. Moreover, we demonstrate that lipoglycans can bind cell surface-expressed TLR2 and that their ability to induce signaling might be, at least in part, dictated by their avidity for the receptor. Finally, our data suggest that lipoglycans and lipoproteins have a common binding site. The present results are thus discussed in the light of the recently published crystal structure of a TLR1-TLR2-lipopeptide complex.

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Section: Activation Of Thp-1 Cellsmentioning

confidence: 71%

Section: Activation Of Thp-1 Cellsmentioning

confidence: 99%

Section: Activation Of Hek-tlr2 Cellsmentioning

confidence: 99%

mentioning

confidence: 99%

“…1). These different lipoglycan variants, either LAM or LM, show variable TLR2-dependent proinflammatory activities (15,16).…”

mentioning

confidence: 99%

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Mannan Chain Length Controls Lipoglycans Signaling via and Binding to TLR2

Nigou¹,

Vasselon²,

Ray³

et al. 2008

The Journal of Immunology

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Corynebacteriales ord. nov.

Goodfellow

Jones

2015

Bergey's Manual of Systematics of Archaea and Bacteria

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Analysis of carbohydrates and glycoconjugates by matrix‐assisted laser desorption/ionization mass spectrometry: An update for the period 2005–2006

Harvey

2010

Mass Spectrometry Reviews

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This review is the fourth update of the original review, published in 1999, on the application of MALDI mass spectrometry to the analysis of carbohydrates and glycoconjugates and brings coverage of the literature to the end of 2006. The review covers fundamental studies, fragmentation of carbohydrate ions, method developments, and applications of the technique to the analysis of different types of carbohydrate. Specific compound classes that are covered include carbohydrate polymers from plants, N- and O-linked glycans from glycoproteins, glycated proteins, glycolipids from bacteria, glycosides, and various other natural products. There is a short section on the use of MALDI-TOF mass spectrometry for the study of enzymes involved in glycan processing, a section on industrial processes, particularly the development of biopharmaceuticals and a section on the use of MALDI-MS to monitor products of chemical synthesis of carbohydrates. Large carbohydrate-protein complexes and glycodendrimers are highlighted in this final section.

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A Lipomannan Variant with Strong TLR-2-dependent Pro-inflammatory Activity in Saccharothrix aerocolonigenes

Cited by 25 publications

References 52 publications

Mannan Chain Length Controls Lipoglycans Signaling via and Binding to TLR2

Mannan Chain Length Controls Lipoglycans Signaling via and Binding to TLR2

Corynebacteriales ord. nov.

Analysis of carbohydrates and glycoconjugates by matrix‐assisted laser desorption/ionization mass spectrometry: An update for the period 2005–2006

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