1. CCL17 controls mast cells for the defense against filarial larval entry.
- Author
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Specht S, Frank JK, Alferink J, Dubben B, Layland LE, Denece G, Bain O, Förster I, Kirschning CJ, Martin C, and Hoerauf A
- Subjects
- 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 metabolism, Dendritic Cells immunology, Dendritic Cells metabolism, Female, Filariasis genetics, Filariasis parasitology, 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 physiology, Mice, Mice, Inbred C3H, Mice, Knockout, Microscopy, Confocal, Skin immunology, Skin metabolism, Time Factors, Wolbachia immunology, Chemokine CCL17 immunology, Filariasis immunology, Filarioidea immunology, Mast Cells immunology
- 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.
- Published
- 2011
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