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Immunity. 2017 May 16;46(5):863-874.e4. doi: 10.1016/j.immuni.2017.04.017.

Mast Cells Are Crucial for Induction of Group 2 Innate Lymphoid Cells and Clearance of Helminth Infections.

Author information

1
Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences, Kanagawa 230-0045, Japan.
2
Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences, Kanagawa 230-0045, Japan; Division of Immunobiology, Department of Medical Life Science, Graduate School of Medical Life Science, Yokohama City University, Kanagawa 230-0045, Japan.
3
Department of Tropical Medicine, The Jikei University School of Medicine, Tokyo 105-8461, Japan.
4
Department of Parasitology, Graduate School of Medicine, Gunma University, Gunma 371-8511, Japan.
5
Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
6
Laboratory of Allergic Diseases, Institute for Advanced Medical Sciences, and Department of Immunology, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
7
Department of Immunology, Institute of Advanced Medicine, Wakayama Medical University, Wakayama 641-8509, Japan.
8
Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences, Kanagawa 230-0045, Japan; Division of Immunobiology, Department of Medical Life Science, Graduate School of Medical Life Science, Yokohama City University, Kanagawa 230-0045, Japan. Electronic address: hiroshi.ohno@riken.jp.

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.

KEYWORDS:

IL-33; ILC2; helminth infection; mast cells; mucosal immunology

PMID:
28514691
DOI:
10.1016/j.immuni.2017.04.017
[Indexed for MEDLINE]
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