Institute of Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany.
Microbes Infect. 2011 Sep;13(10):828-36. doi: 10.1016/j.micinf.2011.04.006. Epub 2011 May 12.
A severe complication of Plasmodium infection is cerebral malaria, a condition mainly attributed to overwhelming inflammatory immune reactions of the host. Murine models differing in susceptibility to experimental cerebral malaria (ECM) allow detailed studies of the host response. We show that ECM- resistant BALB/c mice were driven into interferon gamma- and IL-12-dependent ECM and subsequent death if they received CpG-oligonucleotides after Plasmodium berghei ANKA (PbA) infection. CpG application triggered production of pro-inflammatory cytokines systemically as well in spleen and brain and induced neuropathological symptoms, leading to increased mortality. Experiments with genetically deficient mice confirmed the role of IFN-γ and IL-12 during CpG-triggered immunopathology. Furthermore, the application of CpG and downstream production of pro-inflammatory cytokines contributed to the break down of the blood brain barrier visualized by Evan's Blue, comparable to PbA-infected C57BL/6 mice. Taken together, resistance of BALB/c mice towards ECM development could be altered through induction of pro-inflammatory cytokines by CpG. Therefore, approaches discussed earlier to induce pro-inflammatory immune reactions for malaria protection should be considered with caution.
疟原虫感染的一种严重并发症是脑型疟疾，主要归因于宿主过度的炎症免疫反应。对实验性脑型疟疾（ECM）易感性不同的小鼠模型允许对宿主反应进行详细研究。我们表明，如果在感染疟原虫伯氏疟原虫 ANKA（PbA）后接受 CpG 寡核苷酸，对 ECM 具有抗性的 BALB/c 小鼠会被驱动进入干扰素 γ 和 IL-12 依赖性 ECM 并随后死亡。CpG 应用会引发全身以及脾脏和大脑中促炎细胞因子的产生，并诱导神经病理学症状，导致死亡率增加。用基因缺陷小鼠进行的实验证实了 IFN-γ 和 IL-12 在 CpG 触发的免疫病理学中的作用。此外，CpG 的应用及其下游促炎细胞因子的产生有助于通过 Evan's Blue 可视化血脑屏障的破坏，类似于 PbA 感染的 C57BL/6 小鼠。总之，通过 CpG 诱导促炎细胞因子，BALB/c 小鼠对 ECM 发展的抗性可以改变。因此，应该谨慎考虑之前为诱导抗疟疾的促炎免疫反应而提出的方法。
