Incorporation of Mycobacterium tuberculosis lipoarabinomannan into macrophage membrane rafts is a prerequisite for the phagosomal maturation block.
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.
Welin
Amanda
A
Medical Microbiology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, SE-58185 Linköping, Sweden.
Winberg
Martin E
ME
Abdalla
Hana
H
Särndahl
Eva
E
Rasmusson
Birgitta
B
Stendahl
Olle
O
Lerm
Maria
M
D002454:Cell Differentiation; D017261:Glycosylphosphatidylinositols / Q000378:metabolism; D006801:Humans; D008070:Lipopolysaccharides / Q000378:metabolism*; D008262:Macrophage Activation; D008264:Macrophages / Q000166:cytology* / Q000382:microbiology; D008358:Mannose; D021962:Membrane Microdomains / Q000378:metabolism*; D009000:Monocytes / Q000382:microbiology; D009169:Mycobacterium tuberculosis / Q000378:metabolism / Q000472:pathogenicity*
D017261:Glycosylphosphatidylinositols; D008070:Lipopolysaccharides; C050016:lipoarabinomannan; D008358:Mannose