title: CCL17 controls mast cells for the defense against filarial larval entry.
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.
authors.affiliation: Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, 53105 Bonn, Germany. specht@microbiology-bonn.de
authors.forename: Sabine
authors.initials: S
authors.lastname: Specht
authors.forename: Jutta K
authors.initials: JK
authors.lastname: Frank
authors.forename: Judith
authors.initials: J
authors.lastname: Alferink
authors.forename: Bettina
authors.initials: B
authors.lastname: Dubben
authors.forename: Laura E
authors.initials: LE
authors.lastname: Layland
authors.forename: Gaelle
authors.initials: G
authors.lastname: Denece
authors.forename: Odile
authors.initials: O
authors.lastname: Bain
authors.forename: Irmgard
authors.initials: I
authors.lastname: Förster
authors.forename: Carsten J
authors.initials: CJ
authors.lastname: Kirschning
authors.forename: Coralie
authors.initials: C
authors.lastname: Martin
authors.forename: Achim
authors.initials: A
authors.lastname: Hoerauf
mesh_terms: D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D002199:Capillary Permeability / Q000276:immunology; D015550:Cell Degranulation / Q000276:immunology; D002478:Cells, Cultured; D054414:Chemokine CCL17 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005260:Female; D005368:Filariasis / Q000235:genetics / Q000276:immunology* / Q000469:parasitology; D005370:Filarioidea / Q000276:immunology* / Q000382:microbiology / Q000502:physiology; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006790:Host-Parasite Interactions / Q000276:immunology; D007814:Larva / Q000276:immunology / Q000382:microbiology / Q000502:physiology; D008168:Lung / Q000276:immunology / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D008407:Mast Cells / Q000276:immunology* / Q000502:physiology; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D012867:Skin / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D020577:Wolbachia / Q000276:immunology
chemical_list: D000947:Antigens, Helminth; C499538:Ccl17 protein, mouse; D054414:Chemokine CCL17; D049452:Green Fluorescent Proteins