Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Center for Vaccine Biology and Immunology, Department of Microbiology and Immunology, University of Rochester, Rochester, New York, USA.
Infect Immun. 2020 Mar 23;88(4). 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.
啮齿动物通过捕食在将 传播给最终的猫科宿主中起着至关重要的作用，这种关系已被广泛研究作为对寄生虫免疫反应的模型。 是反刍动物和犬类的密切相关的球虫寄生虫，但不能通过啮齿动物自然传播。我们比较了小鼠对 和 的先天免疫反应，发现在感染后 24 小时内（hpi），细胞因子水平和寄生虫生长动力学存在明显差异。早在感染后 4 小时， 感染的小鼠就产生了明显更高水平的白细胞介素 12（IL-12）和干扰素 γ（IFN-γ），但在感染后的前 24 小时内， 感染的小鼠中的 IFN-γ 水平显著降低或无法检测到。在 MyD88 小鼠中未检测到“立即”产生 IFN-γ 和 IL-12p40。然而，与 IL-12p40 和 IFN-γ 小鼠不同，MyD88 小鼠在本研究中使用的剂量下能够存活 感染。寄生虫负荷的连续测量表明，MyD88 小鼠比野生型（WT）小鼠更容易感染 ，寄生虫负荷的控制与在没有检测到 IL-12 的情况下感染后 3 至 4 天出现的血清 IFN-γ脉冲相关。立即 IFN-γ部分依赖于 小鼠丝状蛋白受体 Toll 样受体 11（TLR11），但 丝状蛋白的异位表达对早期 IFN-γ 产生或寄生虫增殖没有影响。我们的数据表明， 能够在感染后最初几个小时内逃避宿主检测，而 则不能，这可能是由于早期 MyD88 依赖性识别除丝状蛋白以外的配体。
