Immunity
Volume 29, Issue 2, 15 August 2008, Pages 306-317
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Article
Gr1+ Inflammatory Monocytes Are Required for Mucosal Resistance to the Pathogen Toxoplasma gondii

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Summary

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.

CELLIMMUNO

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Present Address: LBCT, CBB, UENF, Campos dos Goytacazes, RJ 28013-602, Brazil

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These authors contributed equally to this work