title: Mast cells orchestrate type 2 immunity to helminths through regulation of tissue-derived cytokines.
abstract: Mast cells (MCs) are potent inflammatory cells that are distributed throughout mucosal barrier tissues and respond rapidly to pathogenic stimuli. During helminth infections, MCs play an important role as late-stage effectors. However, it is currently unknown whether MCs contribute to the early innate events that determine the priming of adaptive immunity. MC-deficient mouse strains and mice treated with the MC stabilizing agent cromolyn sodium had dramatically reduced Th2 priming and type 2 cytokine production and harbored increased parasite burdens following infection with gastrointestinal helminths (Heligmosomoides polygyrus bakeri and Trichuris muris). In addition, early production of the tissue-derived cytokines IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) was significantly diminished in MC-deficient mice and resulted in decreased numbers of infection-elicited IL-25-dependent (Lin(-)CD45(-))CD34(+)Sca-1(+) progenitors, which produced type 2 cytokines and could be differentiated into mast cells ex vivo. Finally, repair of MC deficiency increased production of IL-25, IL-33, and TSLP, restored progenitor cell numbers and Th2 priming, and reduced parasite burden. Our data reveal an innate IgE-independent role for MCs in orchestrating type 2 immune responses via the regulation of IL-25, IL-33, and TSLP.
authors.affiliation: Institute of Molecular Parasitology, Humboldt University of Berlin, D-10115 Berlin, Germany. matthew.hepworth@hu-berlin.de
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Hepworth
authors.forename: Emilia
authors.initials: E
authors.lastname: Daniłowicz-Luebert
authors.forename: Sebastian
authors.initials: S
authors.lastname: Rausch
authors.forename: Martin
authors.initials: M
authors.lastname: Metz
authors.forename: Christian
authors.initials: C
authors.lastname: Klotz
authors.forename: Marcus
authors.initials: M
authors.lastname: Maurer
authors.forename: Susanne
authors.initials: S
authors.lastname: Hartmann
mesh_terms: D000818:Animals; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology*; D006376:Helminths / Q000276:immunology*; D007422:Intestines / Q000469:parasitology; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D016207:Cytokines