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

Abstract

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-γ) by as early as 4 hpi, but the level of IFN-γ was significantly lower or undetectable in T. gondii-infected mice during the first 24 hpi. “Immediate” IFN-γ and IL-12p40 production was not detected in MyD88−/− mice. However, unlike IL-12p40−/− and IFN-γ−/− 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-γ at 3 to 4 days postinfection in the absence of detectable IL-12. Immediate IFN-γ 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-γ 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.

Toxoplasmosis and Relation with Some Immunological Markers for Aborted Women in Thi-Qar Province

“…While IFN-gamma can protect cattle from abortion, high levels of IFN-gamma at the maternal-fetal interface increase fetal death. IFN-gamma is required for the acute control of T. gondii and is dependent on IFN-gamma-driven, cell-mediated immune (CMI) responses, with IFN gamma produced primarily by (IL-12)-stimulated natural killer (NK) cells and T lymphocytes (Coombs et al, 2020).…”

Toxoplasma gondii GRA28 Is Required for Placenta-Specific Induction of the Regulatory Chemokine CCL22 in Human and Mouse

“…This plasmid drives protein expression using the highly active GRA1 promoter. TgRHΔ HPT or N. caninum Liverpool (NcLIVΔ HPT ) ( 54 ) parasites were transfected with ∼40 to 60 μg of GRA28 exon 1 plasmid, and cells were grown overnight in normal medium. For analysis of transiently transfected parasites, cells were only grown for 18 h posttransfection, while for stable transfection, parasites were grown for 2 to 3 passages in medium containing 50 μg/ml of mycophenolic acid and xanthine.…”

A Comparison of Stage Conversion in the Coccidian Apicomplexans Toxoplasma gondii, Hammondia hammondi, and Neospora caninum

“…It is also thought that IFN-γ may play a critical role in cystogenesis. It is hypothesized that IFN-γ contributes to the initiation of tissue cyst formation in vivo, as it can induce cystogenesis in vitro (described above), however IFN-γ knockout mice fail to control acute proliferation of parasites and succumb to acute infection ( Suzuki et al, 1988 ; Suzuki et al, 1989 ) even when infected with avirulent strains of T. gondii ( Coombs et al, 2020 ) making it difficult to determine if IFN-γ induces cystogenesis in vivo. It is also possible that T. gondii spontaneously forms tissue cysts during in vivo infections, however this spontaneous development is again challenging to observe experimentally due to the lethality of T. gondii infections in mice with disrupted immune systems.…”