Gr1(+) inflammatory monocytes are required for mucosal resistance to the pathogen Toxoplasma gondii.
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.
Dunay
Ildiko R
IR
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Damatta
Renato A
RA
Fux
Blima
B
Presti
Rachel
R
Greco
Suellen
S
Colonna
Marco
M
Sibley
L David
LD
D000818:Animals; D018932:Chemokine CCL2 / Q000172:deficiency / Q000276:immunology / Q000378:metabolism*; D016207:Cytokines / Q000097:blood; D018928:Immunity, Mucosal; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000276:immunology / Q000469:parasitology; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D054390:Receptors, CCR2 / Q000172:deficiency / Q000276:immunology / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D014122:Toxoplasma / Q000276:immunology*; D014124:Toxoplasmosis, Animal / Q000276:immunology* / Q000469:parasitology / Q000473:pathology
C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; D016207:Cytokines; D054390:Receptors, CCR2