Interleukin-17/interleukin-17 receptor-mediated signaling is important for generation of an optimal polymorphonuclear response against Toxoplasma gondii infection

Abstract

We investigated the role of interleukin-17 (IL-17)/IL-17 receptor (IL-17R)-mediated signaling in the protective immunity against Toxoplasma gondii. IL-17R(-/-) mice developed a normal adaptive immunity against the parasite. However, increased mortality in the knockout animals can be attributed to a defect in the migration of polymorphonuclear leukocytes to infected sites during early infection.

FIG. 1.

IL-17R^−/− mice are susceptible to oral T. gondii infection and display a high parasite burden. Survival of IL-17R^−/− mice infected with different doses of cysts (15 [A] or 30 [B] cysts/mouse) is shown. Data are represented as the cumulative percentage of two experiments (n = 10). The statistical analysis was performed using the Kaplan-Meier test (16). Shown is the number of parasites per microgram of tissue DNA in the organs of IL-17R^−/− mice infected with 15 (C) or 30 (D) cysts of T. gondii (n = 3). Statistical analysis was performed using an unpaired Student's t test as already described (12).

FIG. 2.

Photomicrographs of the liver and ileum from IL-17R^−/− and wild-type mice infected with 30 cysts of T. gondii at day 7 p.i. (A) Wild-type (WT) liver: extensive fatty change is seen in hepatocytes with small foci of mixed PMN and lymphocytic infiltration. Bar, 10 μM. (B) IL17R^−/− liver: less severe fatty change is seen in hepatocytes with lymphocytic inflammation similar to that seen in the parental animals, including some PMNs. Bar, 10 μM. (C) WT small intestine: extensive necrosis and hemorrhage, with loss of the superficial mucosa and blood and cellular debris in bowel lumen (star). Small foci of mixed inflammatory cells including PMNs are seen in the lamina propria (arrow). Bar, 75 μM. (D) IL 17R^−/− small intestine: the superficial mucosa is preserved (star), and a mixed inflammatory infiltrate including PMNs is evident within the lamina propria (arrow). Bar, 75 μM. (Inset) Close-up with arrow pointing to tachyzoites in lamina propria of a knockout animal.

FIG. 3.

Defective PMN influx in IL-17R^−/− mice early after T. gondii infection. The number of neutrophils was determined by differential counting. *, P < 0.05. The results are representative of two experiments.

FIG. 4.

Defective chemokine production in IL-17R^−/− mice infected with T. gondii. IL-17R^−/− mice (three mice/group) were infected with 15 cysts of T. gondii. Data are presented as means ± standard deviations of individual mice. Significant differences between treatment pairs are indicated by lines. **, P < 0.02; *, P ≤ 0.05. The assay was performed twice with similar results.