Mannosylated lipoarabinomannans inhibit IL-12 production by human dendritic cells: evidence for a negative signal delivered through the mannose receptor.
IL-12 is a key cytokine in directing the development of type 1 Th cells, which are critical to eradicate intracellular pathogens such as Mycobacterium tuberculosis. Here, we report that mannose-capped lipoarabinomannans (ManLAMs) from Mycobacterium bovis bacillus Calmette-Guérin and Mycobacterium tuberculosis inhibited, in a dose-dependent manner, the LPS-induced IL-12 production by human dendritic cells. The inhibitory activity was abolished by the loss of the mannose caps or the GPI acyl residues. Mannan, which is a ligand for the mannose receptor (MR) as well as an mAb specific for the MR, also inhibited the LPS-induced IL-12 production by dendritic cells. Our results indicate that ManLAMs may act as virulence factors that contribute to the persistence of M. bovis bacillus Calmette-Guérin and M. tuberculosis within phagocytic cells by suppressing IL-12 responses. Our data also suggest that engagement of the MR by ManLAMs delivers a negative signal that interferes with the LPS-induced positive signals delivered by the Toll-like receptors.
Nigou
J
J
Institut de Pharmacologie et de Biologie Structurale, Centre National de la Recherche Scientifique, Toulouse, France.
Zelle-Rieser
C
C
Gilleron
M
M
Thurnher
M
M
Puzo
G
G
D002240:Carbohydrate Sequence; D002478:Cells, Cultured; D005591:Chemical Fractionation; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D004306:Dose-Response Relationship, Immunologic; D017261:Glycosylphosphatidylinositols / Q000737:chemistry / Q000276:immunology; D006801:Humans; D018664:Interleukin-12 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000378:metabolism; D037181:Lectins, C-Type; D008070:Lipopolysaccharides / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism*; D008351:Mannans / Q000378:metabolism; D008358:Mannose / Q000378:metabolism*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D008969:Molecular Sequence Data; D009163:Mycobacterium bovis / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000276:immunology; D011956:Receptors, Cell Surface / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology*
D017261:Glycosylphosphatidylinositols; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D008351:Mannans; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; C050016:lipoarabinomannan; D018664:Interleukin-12; D008358:Mannose