Immediate Interferon Gamma Induction Determines Murine Host Compatibility Differences between Toxoplasma gondii and Neospora caninum

Rodents are critical for the transmission of Toxoplasma gondii to the definitive feline host via predation, and this relationship has been extensively studied as a model for immune responses to parasites. Neospora caninum is a closely related coccidian parasite of ruminants and canines but is not naturally transmitted by rodents. We compared mouse innate immune responses to N. caninum and T. gondii and found marked differences in cytokine levels and parasite growth kinetics during the first 24 h postinfection (hpi). N. caninum-infected mice produced significantly higher levels of interleukin-12 (IL-12) and interferon gamma (IFN-gamma) by as early as 4 hpi, but the level of IFN-gamma was significantly lower or undetectable in T. gondii-infected mice during the first 24 hpi. Immediate IFN-gamma and IL-12p40 production was not detected in MyD88(-/-) mice. However, unlike IL-12p40 (-/-) and IFN-gamma(-/-) mice, MyD88(-/-) mice survived N. caninum infections at the dose used in this study. Serial measures of parasite burden showed that MyD88(-/-) mice were more susceptible to N. caninum infections than wild-type (WT) mice, and control of parasite burdens correlated with a pulse of serum IFN-gamma at 3 to 4 days postinfection in the absence of detectable IL-12. Immediate IFN-gamma was partially dependent on the T. gondii mouse profilin receptor Toll-like receptor 11 (TLR11), but the ectopic expression of N. caninum profilin in T. gondii had no impact on early IFN-gamma production or parasite proliferation. Our data indicate that T. gondii is capable of evading host detection during the first hours after infection, while N. caninum is not, and this is likely due to the early MyD88-dependent recognition of ligands other than profilin.