title: Mice lacking the chemokine receptor CCR1 show increased susceptibility to Toxoplasma gondii infection.
abstract: Chemokines are critical for the recruitment of effector immune cells to sites of infection. Mice lacking the chemokine receptor CCR1 have defects in neutrophil trafficking and proliferation. In the present study, we tested the susceptibility of CCR1 knockout mice to infection with the obligate intracellular protozoan parasite Toxoplasma gondii. In comparison with parental wild-type mice, CCR1(-/-) mice exhibited dramatically increased mortality to T. gondii in association with an increased tissue parasite load. No differences were observed in Ag-specific T cell proliferation or in cytokine responses between mutant and wild-type mice. However, the influx of PMNs to the peripheral blood and to the liver were reduced in CCR1(-/-) mice during early infection. Our results suggest that CCR1-dependent migration of neutrophils to the blood and tissues may have a significant impact in controlling parasite replication.
authors.affiliation: Department of Medicine, Dartmouth Medical School, Lebanon, NH 03756, USA. Ikhan@lsuhsc.edu
authors.forename: I A
authors.initials: IA
authors.lastname: Khan
authors.forename: P M
authors.initials: PM
authors.lastname: Murphy
authors.forename: L
authors.initials: L
authors.lastname: Casciotti
authors.forename: J D
authors.initials: JD
authors.lastname: Schwartzman
authors.forename: J
authors.initials: J
authors.lastname: Collins
authors.forename: J L
authors.initials: JL
authors.lastname: Gao
authors.forename: G R
authors.initials: GR
authors.lastname: Yeaman
mesh_terms: D000818:Animals; D019742:Chemokines, CC / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease; D022781:Hepatocytes / Q000469:parasitology / Q000473:pathology; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics; D007111:Immunity, Cellular / Q000235:genetics; D007958:Leukocyte Count; D008099:Liver / Q000469:parasitology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009336:Necrosis; D009504:Neutrophils / Q000473:pathology; D009569:Nitric Oxide / Q000502:physiology; D009928:Organ Specificity / Q000235:genetics / Q000276:immunology; D054389:Receptors, CCR1; D019707:Receptors, Chemokine / Q000172:deficiency* / Q000235:genetics*; D014122:Toxoplasma / Q000276:immunology; D014124:Toxoplasmosis, Animal / Q000235:genetics* / Q000276:immunology* / Q000401:mortality / Q000469:parasitology
chemical_list: C515300:CCR1 protein, human; C515301:Ccr1 protein, mouse; D019742:Chemokines, CC; D054389:Receptors, CCR1; D019707:Receptors, Chemokine; D009569:Nitric Oxide