1. Mast Cells Are Crucial for Induction of Group 2 Innate Lymphoid Cells and Clearance of Helminth Infections.
- Author
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Shimokawa C, Kanaya T, Hachisuka M, Ishiwata K, Hisaeda H, Kurashima Y, Kiyono H, Yoshimoto T, Kaisho T, and Ohno H
- Subjects
- Adenosine Triphosphate metabolism, Animals, Cell Communication, Cell Differentiation, Disease Models, Animal, Disease Resistance genetics, GATA2 Transcription Factor genetics, GATA2 Transcription Factor metabolism, Gene Expression, Helminthiasis genetics, Immunophenotyping, Interleukin-33 metabolism, Intestinal Mucosa immunology, Intestinal Mucosa metabolism, Intestinal Mucosa parasitology, Intestinal Mucosa pathology, Lymphocyte Subsets cytology, Lymphocyte Subsets metabolism, Male, Mast Cells cytology, Mast Cells metabolism, Mice, Mice, Knockout, Phenotype, Proto-Oncogene Proteins genetics, Proto-Oncogene Proteins metabolism, Receptors, Purinergic P2X7 metabolism, Trans-Activators genetics, Trans-Activators metabolism, Transcription Factors genetics, Transcription Factors metabolism, Helminthiasis immunology, Helminthiasis parasitology, Helminths immunology, Immunity, Innate, Lymphocyte Subsets immunology, Mast Cells immunology
- Abstract
Mast cells are important for eradication of intestinal nematodes; however, their precise mechanisms of action have remained elusive, especially in the early phase of infection. We found that Spi-B-deficient mice had increased numbers of mast cells and rapidly expelled the Heligmosomoides polygyrus (Hp) nematode. This was accompanied by induction of interleukin-13 (IL-13)-producing group 2 innate lymphoid cells (ILC2) and goblet cell hyperplasia. Immediately after Hp infection, mast cells were rapidly activated to produce IL-33 in response to ATP released from apoptotic intestinal epithelial cells. In vivo inhibition of the P2X7 ATP receptor rendered the Spi-B-deficient mice susceptible to Hp, concomitant with elimination of mast cell activation and IL-13-producing ILC2 induction. These results uncover a previously unknown role for mast cells in innate immunity in that activation of mast cells by ATP orchestrates the development of a protective type 2 immune response, in part by producing IL-33, which contributes to ILC2 activation., (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Published
- 2017
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