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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.
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“They are critical for host defense against bacteria such as Staphylococcus aureus 1 and other pathogens like helminths. 2 , 3 , 4”
From Mast cell ontogeny: From fetal development to life‐long health and disease (2023) · cites this paper as [2]
In the citing paper
“In adults, mast cells have important functions in protective immunity from certain bacteria, 1 helminths 2 , 3 , 4 and animal venoms. 6 , 7”
From Mast cell ontogeny: From fetal development to life‐long health and disease (2023) · cites this paper as [2]
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Cites
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Cited by
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Filbey, K. J., Grainger, J. R., Smith, K. A., Boon, L., van Rooijen, N., Harcus, Y., Jenkins, S., Hewitson, J. P., & Maizels, R. M. (2014) · Immunology & Cell Biology · doi:10.1038/icb.2013.109 · Cited by 130
Mast cell ontogeny: From fetal development to life‐long health and disease
Chia, S. L., Kapoor, S., Carvalho, C., Bajénoff, M., & Gentek, R. (2023) · Immunological Reviews · doi:10.1111/imr.13191 · Cited by 60
Innate immunostimulatory properties of allergens and their relevance to food allergy
Ruiter, B., & Shreffler, W. G. (2012) · Seminars in Immunopathology · doi:10.1007/s00281-012-0334-8 · Cited by 47
“Other factors may contribute more to anti-helminth immunity in mice, such as helminth-specific IgG and IgA [39], and IgE-independent mast cell responses [40].”
Understanding the Type 2 Immunity: An Evolving View Beyond Allergic Diseases
Jiménez‐Saiz, R., Iborra, S., Blanco, C., González‐Pérez, R., Nuñez‐Borque, E., Zeyneloglu, C., Babayev, H., Göksel, O., Göksel, T., Khaitov, M., et al. (2026) · Allergy · doi:10.1111/all.70512 · Cited by 2
Metadata
- Authors
- Hepworth, M. R., Daniłowicz-Luebert, E., Rausch, S., Metz, M., Klotz, C., Maurer, M., & Hartmann, S.
- Affiliations
- Institute of Molecular Parasitology, Humboldt University of Berlin, D-10115 Berlin, Germany;
- Department of Dermatology and Allergy, Allergy Centre Charité, Charité University Medicine, D-10117 Berlin, Germany; and
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2012-04-09
- Volume
- 109
- Issue
- 17
- Pages
- 6644-6649
- ISSN
- 0027-8424
- 1091-6490
- Cited by
- 149
- References
- 1
- Language
- en
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- Hepworth, M. R., Daniłowicz-Luebert, E., Rausch, S., Metz, M., Klotz, C., Maurer, M., & Hartmann, S. (2012). Mast cells orchestrate type 2 immunity to helminths through regulation of tissue-derived cytokines. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1112268109
