Gr1+ Inflammatory Monocytes Are Required for Mucosal Resistance to the Pathogen Toxoplasma gondii

Abstract

The enteric pathogen Toxoplasma gondii is controlled by a vigorous innate T helper 1 (Th1) cell response in the murine model. We demonstrated that after oral infection, the parasite rapidly recruited inflammatory monocytes [Gr1+ (Ly6C+, Ly6G−) F4/80+CD11b+CD11c−], which established a vital defensive perimeter within the villi of the ileum in the small intestine. Mice deficient of the chemokine receptor CCR2 or the ligand CCL2 failed to recruit Gr1+ inflammatory monocytes, whereas dendritic cells and resident tissue macrophages remained unaltered. The selective lack of Gr1+ inflammatory monocytes resulted in an inability of mice to control replication of the parasite, high influx of neutrophils, extensive intestinal necrosis, and rapid death. Adoptive transfer of sorted Gr1+ inflammatory monocytes demonstrated their ability to home to the ileum in infected animals and protect Ccr2−/− mice, which were otherwise highly susceptible to oral toxoplasmosis. Collectively, these findings illustrate the critical importance of inflammatory monocytes as a first line of defense in controlling intestinal pathogens.