Interleukin-15-Dependent NKp46+ Innate Lymphoid Cells Control Intestinal Inflammation by Recruiting Inflammatory Monocytes

With the goal in mind to define how interleukin-15 (IL-15) contributes to acute intestinal inflammation, we have used a mouse model of ileitis induced by oral infection with Toxoplasma gondii. We observed that a crosstalk between IL-15 and interleukin-18 (IL-18) promoted intestinal recruitment of inflammatory monocytes, where these cells participated in parasite control but also in tissue damage. A stromal source of IL-15 controlled the development of lamina propria NKp46+NK1.1+ cells, whereas IL-18 produced during T. gondii infection stimulated their production of the chemokine CCL3. In turn, CCL3 attracted inflammatory monocytes via their chemokine receptor CCR1, which was indispensable for their recruitment into the inflamed gut. Collectively, these results identify the IL-15-dependent subset of intestinal NKp46+ cells as an important source of CCL3, which can amplify intestinal inflammation via the recruitment of CCR1+ inflammatory monocytes. Preliminary evidence suggests that this pathway might operate in Crohn's disease. [Display omitted] ► CCR1 is instrumental for intestinal recruitment of inflammatory monocytes ► CCL3 is produced by the intestinal subset of IL-15-dependent NKp46+NK1.1+ cells ► NK cell-dependent CCL3 enhances intestinal recruitment of inflammatory monocytes ► IL-18 stimulates intestinal CCL3 production during T. gondii-induced ileitis