A synthetic peptide derived from the parasite Toxoplasma gondii triggers human dendritic cells' migration

J Leukoc Biol. 2012 Dec;92(6):1241-50. doi: 10.1189/jlb.1211600. Epub 2012 Oct 2.

Abstract

The migration of DCs is a critical function, enabling information to be carried to where the immunological response occurs. Parasites are known to weaken host immunity by interfering with the functions of DCs and thus, may be a source of molecules with immunomodulatory properties. Here, we demonstrate that the soluble protein, GRA5, specific to Toxoplasma gondii, is able to increase the migration of human CD34-DCs toward CCL19. A synthetic Pep29 derived from the GRA5 hydrophilic NT region (Pep29) was found to be internalized by macropinocytosis and to trigger in vitro migration of CD34-DCs via CCR7 expression without activating DCs. Pep29 also induced a decrease in the number of LCs from human skin epidermis. As local depletion of DCs and migration of immature DCs lead to a disruption of the specific innate response, our results highlight the potential of using pathogen-derived synthetic peptides as novel cell modulators with a therapeutic potential to reduce symptoms in inflammatory disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antigens, CD34 / metabolism
  • Antigens, Protozoan / chemistry
  • Antigens, Protozoan / immunology
  • Antigens, Protozoan / metabolism
  • Antigens, Protozoan / pharmacology*
  • Cell Movement / drug effects*
  • Cell Movement / immunology
  • Cells, Cultured
  • Chemokine CCL19 / immunology
  • Chemokine CCL19 / metabolism
  • Dendritic Cells / drug effects*
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Humans
  • Immunophenotyping
  • Langerhans Cells / immunology
  • Langerhans Cells / metabolism
  • MAP Kinase Signaling System
  • Molecular Sequence Data
  • Peptides / chemistry
  • Peptides / immunology
  • Peptides / metabolism
  • Peptides / pharmacology*
  • Pinocytosis / immunology
  • Protein Interaction Domains and Motifs / immunology
  • Protein Sorting Signals
  • Protozoan Proteins / chemistry
  • Protozoan Proteins / immunology
  • Receptors, CCR7 / metabolism
  • Skin / immunology
  • Toxoplasma / chemistry
  • Toxoplasma / immunology*

Substances

  • Antigens, CD34
  • Antigens, Protozoan
  • Chemokine CCL19
  • GRA5 protein, Toxoplasma gondii
  • Pep29 peptide
  • Peptides
  • Protein Sorting Signals
  • Protozoan Proteins
  • Receptors, CCR7