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

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. [Display omitted] •Spi-B-deficient mice are resistant to intestinal helminth infection•Myeloid differentiation is regulated by the Ets transcription factor Spi-B•Mast cells are a potent source of IL-33 and can activate ILC2•The production of IL-33 by mast cells requires their activation through ATP-P2X7 Mast cells are supposed to contribute to protection against helminthic infection in the later phase. Shimokawa and colleagues demonstrate that mast cells play a critical role for activation of ILC2 responsible for parasite expulsion in the early phase.