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Mast cells orchestrate type 2 immunity to helminths through regulation of tissue-derived cytokines
- Hepworth, Matthew R., Daniłowicz-Luebert, Emilia, Rausch, Sebastian, Metz, Martin, Klotz, Christian, Maurer, Marcus, Hartmann, Susanne
- Proceedings of the National Academy of Sciences of the United States of America 2012 v.109 no.17 pp. 6644-6649
- Heligmosomoides polygyrus, Trichuris muris, cytokines, helminths, immune response, mast cells, mice, sodium, stem cells
- 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.