IL-18 activates mucosal group 2 innate lymphoid cells following enteric bacterial infection

Group 2 innate lymphoid cells (ILC2s) are traditionally associated with immune responses to helminth infection and mediating allergic inflammation via the production of type 2 cytokines. However, little is currently known about activation of ILC2s in response to bacterial infection. Here we show that colonic lamina propria ILC2s proliferate in response to infection with the enteric mouse pathogen Citrobacter rodentium , which is used to model infections with enteropathogenic and enterohaemorrhagic Escherichia coli . We also show that following infection, the colonic lamina propria ILC2s secret IL-4, IL-5 and IL-13. We demonstrate that, in addition to IL-33, colonic ILC2s are activated by IL-18, with both cytokines being upregulated in C. rodentium- infected gut. Whilst C. rodentium did not induce ILC2 proliferation in IL-22 KO mice, this was reversed by administration of IL-18. Conversely, injection of IL-18 binding protein into C. rodentium- infected wild type mice blocked activation of ILC2s. These data show that ILC2s are activated in response to bacterial gut infection, where proliferation and activation of ILC2s can be mediated via IL-18 induced by IL-22 signalling.