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

Chikako Shimokawa; Takashi Kanaya; Masami Hachisuka; Kenji Ishiwata; Hajime Hisaeda; Yosuke Kurashima; Hiroshi Kiyono; Tomohiro Yoshimoto; Tsuneyasu Kaisho; Hiroshi Ohno

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

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

Authors

Affiliations

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.

PMID: 28514691
DOI: 10.1016/j.immuni.2017.04.017

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

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
Helminthiasis / immunology*
Helminthiasis / parasitology*
Helminths / immunology*
Immunity, Innate*
Immunophenotyping
Interleukin-33 / metabolism
Intestinal Mucosa / immunology
Intestinal Mucosa / metabolism
Intestinal Mucosa / parasitology
Intestinal Mucosa / pathology
Lymphocyte Subsets / cytology
Lymphocyte Subsets / immunology*
Lymphocyte Subsets / metabolism
Male
Mast Cells / cytology
Mast Cells / immunology*
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

Substances

GATA2 Transcription Factor
Interleukin-33
Proto-Oncogene Proteins
Receptors, Purinergic P2X7
Trans-Activators
Transcription Factors
proto-oncogene protein Spi-1
Adenosine Triphosphate