Immunology · 2004 · 67 citations · 25 references
Life SciencesImmunologyMolecular BiologyImmunoregulationInflammationInnate ImmunityDendritic Cell BiologyDendritic Cell RegulationInflammation In Infectious DiseaseInflammatory Cell ResponsesInflammatory SignalingMacrophage BiologyBone Marrow - Derived CellsDendritic Cell Inflammatory ResponsesDendritic Cell-t Cell InteractionEx Vivo ModelsImmune System ModulationImmunosuppressive FunctionMacrophage ImmunomodulationTh2 Immune Response
We have previously shown in an in vitro study that the filarial nematode phosphorylcholine (PC)-containing glycoprotein ES-62 promotes a murine dendritic cell (DC) phenotype that induces T helper type 2 (Th2) responses. We now show that, in addition to directly priming Th2 responses, ES-62 can act to dampen down the pro-inflammatory DC responses elicited by lipopolysaccharide. Furthermore, we also demonstrate that murine DCs and macrophages derived ex vivo from bone marrow cells exposed in vivo to ES-62 by release from osmotic pumps are hyporesponsive to subsequent stimulation with lipopolysaccharide. These effects can be largely mimicked by exposure to the PC moiety of ES-62 conjugated to an irrelevant protein. The data we provide are, as far as we aware, the first to show that a defined pathogen product can modulate the developmental pathway of bone marrow cells of the immune system in vivo. Such a finding could have important implications for the use of pathogen products or their derivatives for immunotherapy.
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