CXCR2 deficiency confers impaired neutrophil recruitment and increased susceptibility during Toxoplasma gondii infection.
Neutrophil migration to the site of infection is a critical early step in host immunity to microbial pathogens, in which chemokines and their receptors play an important role. In this work, mice deficient in expression of the chemokine receptor CXCR2 were infected with Toxoplasma gondii and the outcome was monitored. Gene-deleted animals displayed completely defective neutrophil recruitment, which was apparent at 4 h and sustained for at least 36 h. Kit(W)/Kit(W-v) animals also displayed defective polymorphonuclear leukocyte migration, suggesting mast cells as one source of chemokines driving the response. Tachyzoite infection and replication were accelerated in CXCR2(-/-) animals, resulting in establishment of higher cyst numbers in the brain relative to wild-type controls. Furthermore, serum and spleen cell IFN-gamma levels in infected, gene-deleted mice were reduced 60-75% relative to infected normal animals, and spleen cell TNF-alpha was likewise reduced by approximately 50%. These results highlight an important role for CXCR2 in neutrophil migration, which may be important for early control of infection and induction of immunity during Toxoplasma infection.
Del Rio
L
L
Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
Bennouna
S
S
Salinas
J
J
Denkers
E Y
EY
D000818:Animals; D027682:Cation Transport Proteins / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis / Q000172:deficiency; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D008407:Mast Cells / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D020556:Neutrophil Infiltration / Q000235:genetics* / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D015513:Oncogene Proteins / Q000235:genetics; D010529:Peritoneal Cavity / Q000473:pathology; D019009:Proto-Oncogene Proteins c-kit; D023063:Receptors, Interleukin-8B / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D014122:Toxoplasma / Q000254:growth & development / Q000276:immunology*; D014124:Toxoplasmosis, Animal / Q000235:genetics* / Q000276:immunology* / Q000469:parasitology; D000099173:Natural Resistance-associated Macrophage Protein 1
D027682:Cation Transport Proteins; D016207:Cytokines; D015513:Oncogene Proteins; D019009:Proto-Oncogene Proteins c-kit; D023063:Receptors, Interleukin-8B; D000099173:Natural Resistance-associated Macrophage Protein 1