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

A. K. Shabaana, K. Kulangara, I. Semac, Y. Parel, S. Ilangumaran, K. Dharmalingam, C. Chizzolini, D. C. Hoessli

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

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-γ) and increasing type 2 (IL-4 and IL-5) cytokine production. Modification by the mannosecapped 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.

Original languageEnglish
Pages (from-to)179-187
Number of pages9
JournalCellular and Molecular Life Sciences
Volume62
Issue number2
DOIs
StatePublished - Jan 2005

Keywords

  • Cytokine
  • Lipoarabinomannan
  • Raft
  • Signalling
  • Th1/Th2

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