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Title

Mycobacterial lipoarabinomannans modulate cytokine production in human T helper cells by interfering with raft/microdomain signalling
Authors
Shabaana, A. K.
Kulangara, Karina
Semac, Isabelle
Parel, Yann
Ilangumaran, Subburaj
Dharmalingam, K.
Chizzolini, Carlo
Hoessli, Daniel
Published in Cellular and Molecular Life Sciences. 2005, vol. 62, no. 2, p. 179-187
Abstract Lipoarabinomannans (LAMs) are major lipoglycans of the mycobacterial envelope and constitute immunodominant epitopes of mycobacteria. In this paper, we show that mannose-capped (ManLAM) and non-mannose-capped (PILAM) mycobacterial lipoglycans insert into T helper cell rafts without apparent binding to known receptors. T helper cells modified by the insertion of PILAM responded to CD3 cross-linking by decreasing type 1 (IL-2 and IFN-gamma) and increasing type 2 (IL-4 and IL-5) cytokine production. Modification by the mannose-capped ManLAMs had similar, but more limited effects on T helper cell cytokine production. When incorporated into isolated rafts, PILAMs modulated membrane-associated kinases in a dose-dependent manner, inducing increased phosphorylation of Src kinases and Cbp/PAG in Th1 rafts, while decreasing phosphorylation of the same proteins in Th2 rafts. Mycobacterial lipoglycans thus modify the signalling machineries of rafts/microdomains in T helper cells, a modification of the membrane organization that eventually leads to an overall enhancement of type 2 and inhibition of type 1 cytokine production.
Keywords Base Sequence — Cytokines/ biosynthesis — Humans — Interleukins/metabolism — Lipopolysaccharides/ pharmacology — Mannose/chemistry/metabolism — Membrane Glycoproteins/chemistry/metabolism — Membrane Microdomains/chemistry/ metabolism — Molecular Sequence Data — Mycobacterium/chemistry/ immunology — Signal Transduction — Th1 Cells/chemistry/ immunology — Th2 Cells/chemistry/ immunology
Identifiers
PMID: 15666089
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Other version: http://www.springerlink.com/content/377lj5c7djnxb1qx/
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(ISO format) 		SHABAANA, A. K. et al. Mycobacterial lipoarabinomannans modulate cytokine production in human T helper cells by interfering with raft/microdomain signalling. In: Cellular and Molecular Life Sciences, 2005, vol. 62, n° 2, p. 179-187. https://archive-ouverte.unige.ch/unige:11069

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Deposited on : 2010-08-27

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