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

Abstract

Summary The enteric pathogen Toxoplasma gondii is controlled by a vigorous innate Th1 response in the murine model. We demonstrate that following oral infection the parasite rapidly recruits inflammatory monocytes (Gr1+ Ly6C+ Ly6G− F4/80+ CD11b+ CD11c−), which establish a vital defensive perimeter within the villi of the ileum in the small intestine. Knock out mice lacking the chemokine receptor CCR2 or the ligand MCP-1, failed to recruit Gr1+ (Ly6C+) inflammatory monocytes, while dendritic cells and resident tissue macrophages remained unaltered. The selective lack of Gr1+ (Ly6C+) inflammatory monocytes resulted in an inability to control replication of the parasite, high influx of neutrophils, extensive intestinal necrosis, and rapid death. Adoptive transfer of sorted Gr1+ (Ly6C+) 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.