CX3CR1+ macrophages support IL-22 production by innate lymphoid cells during infection with Citrobacter rodentium

Abstract

Innate immune cells, such as intestinal epithelial cells, dendritic cells (DCs), macrophages, granulocytes, and innate lymphoid cells provide a first line of defence to enteric pathogens. To study the role of CX3CR1 + DCs and macrophages in host defence, we infected CX 3CR1-GFP animals with Citrobacter rodentium. When transgenic CX 3CR1-GFP animals are infected with the natural mouse pathogen C. rodentium, CX3CR1-/- animals showed a delayed clearance of C. rodentium as compared with (age- and sex-matched) wild-type B6 animals. The delayed clearance of C. rodentium is associated with reduced interleukin (IL)-22 expression. In C. rodentium-infected CX3CR1-GFP animals, IL-22 producing lymphoid-tissue inducer cells (LTi cells) were selectively reduced in the absence of CX3CR1. The reduced IL-22 expression correlates with decreased expression of the antimicrobial peptides RegIIIβ and RegIIIγ. The depletion of CX3CR1+ cells by diphtheria toxin injection in CX3CR1-GFP × CD11c.DOG animals confirmed the role of CX3CR1+ phagocytes in establishing IL-22 production, supporting the clearance of a C. rodentium infection. © 2013 Society for Mucosal Immunology.