Immunity. 2008 Aug 6. [Epub ahead of print]
Gr1(+) Inflammatory Monocytes Are Required for Mucosal Resistance to the Pathogen Toxoplasma gondii
Dunay IR, Damatta RA, Fux B, Presti R, Greco S, Colonna M, Sibley LD.
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
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.
PMID: 18691912 [PubMed - as supplied by publisher]