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

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

In: Cellular and Molecular Life Sciences CMLS, 2005, vol. 62, no. 2, p. 179-187

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    Titre
    • Mycobacterial lipoarabinomannans modulate cytokine production in human T helper cells by interfering with raft/microdomain signalling
    Auteur
    • Shabaana, A.. Department of Pathology and Immunology, Centre médical universitaire, University of Geneva Medical School, 1 rue Michel-Servet, 1211, Geneva 4, Switzerland
    • Kulangara, K.. Department of Pathology and Immunology, Centre médical universitaire, University of Geneva Medical School, 1 rue Michel-Servet, 1211, Geneva 4, Switzerland
    • Semac, I.. Department of Pathology and Immunology, Centre médical universitaire, University of Geneva Medical School, 1 rue Michel-Servet, 1211, Geneva 4, Switzerland
    • Parel, Y.. Department of Immunology and Allergy, University Hospital, 1211, Geneva 14, Switzerland
    • Ilangumaran, S.. Department of Pathology and Immunology, Centre médical universitaire, University of Geneva Medical School, 1 rue Michel-Servet, 1211, Geneva 4, Switzerland
    • Dharmalingam, K.. School of Biotechnology, Madurai Kamaraj University, 625021, Madurai, India
    • Chizzolini, C.. Department of Immunology and Allergy, University Hospital, 1211, Geneva 14, Switzerland
    • Hoessli, D.. Department of Pathology and Immunology, Centre médical universitaire, University of Geneva Medical School, 1 rue Michel-Servet, 1211, Geneva 4, Switzerland
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • Cellular and Molecular Life Sciences CMLS, 2005, vol. 62, no. 2, p. 179-187. Birkhäuser-Verlag; www.birkhauser.ch
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:320721
    Summary
    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 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