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

Immunology. 2004 Dec;113(4):491-8. doi: 10.1111/j.1365-2567.2004.01993.x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / drug effects
  • Cells, Cultured
  • Cytokines / biosynthesis
  • Dendritic Cells / drug effects*
  • Dendritic Cells / immunology
  • Helminth Proteins / pharmacology*
  • Inflammation / immunology*
  • Infusion Pumps, Implantable
  • Lipopolysaccharides / immunology
  • Macrophages / drug effects*
  • Macrophages / immunology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Myeloid Progenitor Cells / drug effects
  • Myeloid Progenitor Cells / immunology
  • Phosphorylcholine / immunology*

Substances

  • Cytokines
  • ES-62 protein, Acanthocheilonema viteae
  • Helminth Proteins
  • Lipopolysaccharides
  • Phosphorylcholine