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Mycobacterial lipoarabinomannans modulate cytokine production in human T helper cells by interfering with raft/microdomain signalling

Shabaana, A. K.
Kulangara, Karina
Dharmalingam, K.
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 SequenceCytokines/ biosynthesisHumansInterleukins/metabolismLipopolysaccharides/ pharmacologyMannose/chemistry/metabolismMembrane Glycoproteins/chemistry/metabolismMembrane Microdomains/chemistry/ metabolismMolecular Sequence DataMycobacterium/chemistry/ immunologySignal TransductionTh1 Cells/chemistry/ immunologyTh2 Cells/chemistry/ immunology
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PMID: 15666089
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