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Protective and pathological roles of mast cells and basophils

Key Points

  • Mast cells and basophils are phenotypically and functionally related cell types that promote protective immunity to helminths, but that can also cause pathology during allergic inflammation.

  • Mast cells and basophils might have evolved from a common precursor cell, such as the mast cell/basophil-like (MCBL) cell or the test cell, which were identified in the urochordate Styela plicata. A basophil/mast cell progenitor (BMCP) cell population was isolated from the spleen of adult mice, and the timed expression of the transcription factors GATA-binding protein 2 and CCAAT/enhancer-binding protein-α in these progenitor cells might determine whether they eventually mature into basophils or mast cells.

  • New mouse models have been developed in which mast cells or basophils can be constitutively or conditionally depleted. These models allow more specific targeting of mast cells and basophils, compared with the Kit-mutant mouse strains and depleting antibody strategies which were previously used to assess mast cell and basophil functions in vivo. Therefore, these new mouse models will help to further clarify the true biological roles of basophils and mast cells.

  • Although mast cells and basophils can express interleukin-4, CD40 ligand and low levels of MHC class II under certain conditions, they seem to have no major role in driving the induction of adaptive type 2 immune responses.

  • Mast cells and basophils cooperate to provide protection during secondary infestation with ticks. In addition, both cell types contribute, to various degrees, to protective immunity during gastrointestinal helminth infections in mice.

  • IgE-mediated anaphylaxis is strictly mast cell-dependent, whereas IgG1-mediated anaphylaxis in mice results from the activation of monocytes, neutrophils or basophils. Basophils are recruited to the skin in a mouse model of atopic dermatitis and they induce IgE-mediated chronic allergic inflammation of the skin in the absence of mast cells.

Abstract

Mast cells and basophils are potent effector cells of the innate immune system, and they have both beneficial and detrimental functions for the host. They are mainly implicated in pro-inflammatory responses to allergens but can also contribute to protection against pathogens. Although both cell types were identified more than 130 years ago by Paul Ehrlich, their in vivo functions remain poorly understood. The precursor cell populations that give rise to mast cells and basophils have recently been characterized and isolated. Furthermore, new genetically modified mouse strains have been developed, which enable more specific targeting of mast cells and basophils. Such advances offer new opportunities to uncover the true in vivo activities of these cells and to revisit their previously proposed effector functions.

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Figure 1: Evolution of mast cells and basophils.
Figure 2: Development of mast cells and basophils in the murine bone marrow.
Figure 3: Protective immunity against helminths and ticks.

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Acknowledgements

The author thanks the members of the Voehringer laboratory, R. Maizels and P. Yu for discussions during the preparation of the manuscript and he apologizes to the researchers in the field whose work was not cited owing to space limitations. He further acknowledges the support by the European Research Council starting grant PAS_241506.

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Voehringer, D. Protective and pathological roles of mast cells and basophils. Nat Rev Immunol 13, 362–375 (2013). https://doi.org/10.1038/nri3427

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