Decreased Resistance of TNF Receptor p55- and p75-Deficient Mice to Chronic Toxoplasmosis Despite Normal Activation of Inducible Nitric Oxide Synthase In Vivo

Increased cyst counts and severe necrotizing encephalitis in T. gondii-infected TNF R1/R2-deficient mice. WT and TNF R1/R2-deficient mice were infected i.p. with 20 cysts and brains harvested 15 and 21 days later for histopathology and quantitation of cysts. A, Mean cyst counts and SE are shown for each group of 7 to 11 animals. Cyst counts were significantly different between WT and TNF R1/R2-deficient mice at both time points (p < 0.01). B–E, Photomicrographs of periodic acid Schiff’s-stained brain sections from WT (B) and receptor-deficient mice at 21 days postinfection. C–E, An inflammatory nodule with two dormant cysts (solid arrowheads) is shown in B. Active tachyzoite replication (arrows) and a cyst (solid arrowhead) are evident in the brain of an infected TNF R1/R2-deficient mouse (C). In addition, an extensive area of necrosis (D) with tachyzoites (unfilled arrowheads) in the cellular debris is shown at a higher magnification in E.

IFN-γ and IL-12 p40 synthesis by splenocytes from WT and TNF R1/R2-deficient mice in vitro. Spleen cells were cultured and cytokine levels in supernatant were tested, as detailed in Materials and Methods. Data shown are mean and SE of four to five mice per group. Similar results were obtained in two additional experiments. No statistically significant difference in production of either cytokine between WT and KO cells was observed.

In vitro replication of T. gondii tachyzoites in peritoneal cells harvested from uninfected and 5 day infected TNF R1/R2-deficient or WT mice. Animals were infected with 20 ME49 cysts, and 5 days later peritoneal cells were harvested. The cells were then stimulated with 100 U/ml of IFN-γ or left untreated, infected, and cultured, as described in Materials and Methods. Data shown are representative of three experiments performed.