Neospora caninum infection is an important cause of neuromuscular disease in dogs and abortion in cattle, leading to significant economic losses in beef and dairy industries. The protective immunity against apicomplexan parasites, specifically Toxoplasma gondii and N. caninum, is typically achieved by inducing an IL-12-driven Th1 immune response. IL-12 stimulates IFN-γ production, which activates Inducible Nitric Oxide Synthase (iNOS) and promotes consequent Nitric Oxide (NO) synthesis, classically described as one of the main effector mechanisms for parasite elimination. Here, we aimed to evaluate the role played by iNOS during N. caninum infection. Our results show that N. caninum infection in C57BL/6 wild type (WT) mice induce NO production in vivo and in vitro. In agreement, iNOS deficient mice, as well as WT mice treated with iNOS inhibitor aminoguanidine, succumbed during acute infection with a dose lethal to 50 % of the WT mice, and presented significant increase in parasite load when submitted to sub-lethal infection protocols. Interestingly, the lack of control of parasite proliferation observed in iNOS-/- mice was associated with notable CNS inflammation and increased production of the main systemic proinflammatory cytokines (IL-12, IFN-γ, IL-6, TNF and IL-17A). Taken together, our findings show that iNOS plays an important role in restricting N. caninum replication, while also modulates the inflammatory process induced by the infection.

中文翻译：

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犬新孢子虫感染期间，寄生虫限制和炎症调节需要诱导型一氧化氮合酶。

犬新孢子虫感染是狗神经肌肉疾病和牛流产的重要原因，导致牛肉和奶制品行业的重大经济损失。通常通过诱导IL-12驱动的Th1免疫反应来实现针对apicomplexan寄生虫（特别是弓形虫和犬新孢子虫）的保护性免疫。IL-12刺激IFN-γ的产生，从而激活诱导型一氧化氮合酶（iNOS）并促进随后的一氧化氮（NO）合成，这通常被描述为消除寄生虫的主要效应器机制之一。在这里，我们旨在评估iNOS在犬新孢子虫感染过程中的作用。我们的结果表明，C57BL / 6野生型（WT）小鼠中的犬新孢子虫感染可在体内和体外诱导NO的产生。同意，iNOS缺陷小鼠，以及用iNOS抑制剂氨基胍治疗的WT小鼠在急性感染期间死亡，致死剂量为WT小鼠的50％，并且在接受亚致死性感染方案后，其寄生虫负荷显着增加。有趣的是，在iNOS-/-小鼠中观察不到对寄生虫增殖的控制与明显的中枢神经系统炎症和主要全身促炎性细胞因子（IL-12，IFN-γ，IL-6，TNF和IL-17A）的产生增加有关。 。综上所述，我们的发现表明，iNOS在限制犬新孢子虫的复制中起着重要作用，同时也调节由感染引起的炎症过程。有趣的是，在iNOS-/-小鼠中观察不到对寄生虫增殖的控制与明显的中枢神经系统炎症和主要全身促炎细胞因子（IL-12，IFN-γ，IL-6，TNF和IL-17A）的产生增加有关。 。综上所述，我们的发现表明，iNOS在限制犬新孢子虫的复制中起着重要作用，同时也调节由感染引起的炎症过程。有趣的是，在iNOS-/-小鼠中观察不到对寄生虫增殖的控制与明显的中枢神经系统炎症和主要全身促炎性细胞因子（IL-12，IFN-γ，IL-6，TNF和IL-17A）的产生增加有关。 。综上所述，我们的发现表明，iNOS在限制犬新孢子虫的复制中起着重要作用，同时也调节由感染引起的炎症过程。