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Infection and Immunity, July 2008, p. 2882-2887, Vol. 76, No. 7
0019-9567/08/$08.00+0     doi:10.1128/IAI.01549-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Incorporation of Mycobacterium tuberculosis Lipoarabinomannan into Macrophage Membrane Rafts Is a Prerequisite for the Phagosomal Maturation Block

Amanda Welin, Martin E. Winberg, Hana Abdalla, Eva Särndahl, Birgitta Rasmusson, Olle Stendahl, and Maria Lerm^*

Medical Microbiology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, SE-58185 Linköping, Sweden

Received 23 November 2007/ Returned for modification 10 January 2008/ Accepted 4 April 2008

Lipoarabinomannan (LAM) is one of the key virulence factors for Mycobacterium tuberculosis, the etiological agent of tuberculosis. During uptake of mycobacteria, LAM interacts with the cell membrane of the host macrophage and can be detected throughout the cell upon infection. LAM can inhibit phagosomal maturation as well as induce a proinflammatory response in bystander cells. The aim of this study was to investigate how LAM exerts its action on human macrophages. We show that LAM is incorporated into membrane rafts of the macrophage cell membrane via its glycosylphosphatidylinositol anchor and that incorporation of mannose-capped LAM from M. tuberculosis results in reduced phagosomal maturation. This is dependent on successful insertion of the glycosylphosphatidylinositol anchor. LAM does not, however, induce the phagosomal maturation block through activation of p38 mitogen-activated protein kinase, contradicting some previous suggestions.

Published ahead of print on 21 April 2008.

Editor: J. L. Flynn

Present address: Department of Biomedicine, School of Health and Medical Sciences, Örebro University, SE-701 82 Örebro, Sweden.