CCL17 controls mast cells for the defense against filarial larval entry

J Immunol. 2011 Apr 15;186(8):4845-52. doi: 10.4049/jimmunol.1000612. Epub 2011 Mar 11.

Abstract

Filarial parasites have to trespass many barriers to successfully settle within their mammalian host, which is equipped with mechanical borders and complex weaponry of an evolved immune system. However, little is known about mechanisms of early local events in filarial infections. In this study, bone marrow-derived dendritic cells not only upregulated activation markers CD40 and CD80 upon in vitro stimulation with filarial extracts, but also secreted CCL17, a chemokine known to be produced upon microbial challenge. Mice deficient for CCL17 had an up to 4-fold higher worm burden compared with controls by day 10 of infection with the murine filaria Litomosoides sigmodontis. Also, numbers of mast cells (MCs) invading the skin and degranulation were significantly increased, which was associated with enhanced vascular permeability and larval establishment. This phenotype was reverted by inhibition of MC degranulation with disodium cromoglycate or by blockade of histamine. In addition, we showed that CCL17-mediated vascular permeability was dependent on the presence of Wolbachia endosymbionts and TLR2. Our findings reveal that CCL17 controls filarial larval entry by limiting MC-dependent vascular permeability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Helminth / immunology
  • Bone Marrow Cells / immunology
  • Bone Marrow Cells / metabolism
  • Capillary Permeability / immunology
  • Cell Degranulation / immunology
  • Cells, Cultured
  • Chemokine CCL17 / genetics
  • Chemokine CCL17 / immunology*
  • Chemokine CCL17 / metabolism
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Female
  • Filariasis / genetics
  • Filariasis / immunology*
  • Filariasis / parasitology
  • Filarioidea / immunology*
  • Filarioidea / microbiology
  • Filarioidea / physiology
  • Flow Cytometry
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Host-Parasite Interactions / immunology
  • Larva / immunology
  • Larva / microbiology
  • Larva / physiology
  • Lung / immunology
  • Lung / metabolism
  • Lymph Nodes / immunology
  • Lymph Nodes / metabolism
  • Mast Cells / immunology*
  • Mast Cells / physiology
  • Mice
  • Mice, Inbred C3H
  • Mice, Knockout
  • Microscopy, Confocal
  • Skin / immunology
  • Skin / metabolism
  • Time Factors
  • Wolbachia / immunology

Substances

  • Antigens, Helminth
  • Ccl17 protein, mouse
  • Chemokine CCL17
  • Green Fluorescent Proteins