Citrobacter rodentium infection activates colonic lamina propria group 2 innate lymphoid cells

Group 3 innate lymphoid cells (ILC3s) play a major role in protecting against infection with the enteric mouse pathogenCitrobacter rodentium,used to model infections with enteropathogenic and enterohaemorrhagicEscherichia coli. ILC3s-secreted IL-22, shown to be indispensable for protection againstC. rodentiuminfection, induces secretion of IL-18, antimicrobial peptides and nutritional immunity proteins as well as activation of tissue regeneration processes. While ILC2s have traditionally been associated with immune responses to helminth infection and allergic inflammation via the production of type 2 cytokines (e.g. IL-4, IL-5, IL-9 and IL-13), more recently they have been implicated in protection againstClostridium difficileandHelicobacter pyloriinfections. Here we show that colonic lamina propria ILC2s proliferate in response toC. rodentiuminfection and secrete IL-4, IL-5 and IL-13, which are involved in maintenance of the intestinal barrier function, tissue repair and mucus secretion. When stimulated with IL-18, colonic ILC2s from uninfected naïve mice secreted type 2 cytokines. Injection of IL-18 binding protein (IL18BP), at 2- and 3-days postC. rodentiuminfection, blocked activation of ILC2s. These data show that ILC2s are activated in response to infection with an enteric Gram-negative pathogen, where stimulation with IL-18 plays a role in inducing proliferation and secretion of type 2 cytokines.