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

• Published in: Infection and immunity 2020-03, Vol.88 (4)
• Main Authors: Coombs, Rachel S, Blank, Matthew L, English, Elizabeth D, Adomako-Ankomah, Yaw, Urama, Ifeanyi-Chukwu Samuel, Martin, Andrew T, Yarovinsky, Felix, Boyle, Jon P
• Format: Article
• Language: English
• Subjects: Animals; Coccidiosis - immunology; Immunologic Factors - metabolism; Interferon-gamma - deficiency; Interferon-gamma - metabolism; Interleukin-12 - deficiency; Interleukin-12 - metabolism; Mice; Mice, Knockout; Molecular Pathogenesis; Myeloid Differentiation Factor 88 - deficiency; Myeloid Differentiation Factor 88 - metabolism; Neospora - growth & development; Neospora - immunology; Rodent Diseases - immunology; Survival Analysis; Time Factors; Toxoplasma - growth & development; Toxoplasma - immunology; Toxoplasmosis, Animal - immunology
• ISSN: 0019-9567; 1098-5522; 1098-5522
• DOI: 10.1128/IAI.00027-20

Rodents are critical for the transmission of to the definitive feline host via predation, and this relationship has been extensively studied as a model for immune responses to parasites. is a closely related coccidian parasite of ruminants and canines but is not naturally transmitted by rodents. We compared mouse innate immune responses to and and found marked differences in cytokine levels and parasite growth kinetics during the first 24 h postinfection (hpi). -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 -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 infections at the dose used in this study. Serial measures of parasite burden showed that MyD88 mice were more susceptible to 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 mouse profilin receptor Toll-like receptor 11 (TLR11), but the ectopic expression of profilin in had no impact on early IFN-γ production or parasite proliferation. Our data indicate that is capable of evading host detection during the first hours after infection, while is not, and this is likely due to the early MyD88-dependent recognition of ligands other than profilin.