In vivo exposure of murine dendritic cell and macrophage bone marrow progenitors to the phosphorylcholine-containing filarial nematode glycoprotein ES-62 polarizes their differentiation to an anti-inflammatory phenotype.
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.
Goodridge
Helen S
HS
Division of Immunology, Infection and Inflammation, University of Glasgow, Glasgow, United Kingdom.
Marshall
Fraser A
FA
Wilson
Emma H
EH
Houston
Katrina M
KM
Liew
Foo Y
FY
Harnett
Margaret M
MM
Harnett
William
W
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D015801:Helminth Proteins / Q000494:pharmacology*; D007249:Inflammation / Q000276:immunology*; D015918:Infusion Pumps, Implantable; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D023461:Myeloid Progenitor Cells / Q000187:drug effects / Q000276:immunology; D010767:Phosphorylcholine / Q000276:immunology*
D016207:Cytokines; C435884:ES-62 protein, Acanthocheilonema viteae; D015801:Helminth Proteins; D008070:Lipopolysaccharides; D010767:Phosphorylcholine