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 h ost immunity to microbial pathogens, in which chemokines and their receptor s play an important role. In this work, mice deficient in expression of the chemokine receptor CXCR2 were infected with Toxoplasma gondii and the outc ome was monitored. Gene-deleted animals displayed completely defective neut rophil recruitment, which was apparent at 4 h and sustained for at least 36 h. Kit(W)/Kit(W-v) animals also displayed defective polymorphonuclear leuk ocyte migration, suggesting mast cells as one source of chemokines driving the response. Tachyzoite infection and replication were accelerated in CXCR 2(-/-) animals, resulting in establishment of higher cyst numbers in the br ain 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 similar to 50%. These results highlight an important role for CXCR2 in neu trophil migration, which may be important for early control of infection an d induction of immunity during Toxoplasma infection.