Centre for the Study of Host Resistance, Department of Medicine, McGill University, Montreal, Canada.
Parasite Immunol. 2010 Nov-Dec;32(11-12):773-8. doi: 10.1111/j.1365-3024.2010.01250.x.
To investigate the effect of caspase-12 deficiency on IFN-γ- independent control of blood-stage malaria, we compared lethal Plasmodium yoelii 17XL infection in wild-type C57BL ⁄ 6J and caspase-12-/-mice. Infected caspase-12-/- mice exhibited higher parasitaemia than WT mice on days 8 and 9 post-inoculation, but all WT and caspase-12-/- mice succumbed by day 10. In addition, infected caspase-12-/-mice had significantly elevated levels of IFN-γ, TNF, IL-18,and IL-10 in sera compared to infected WT mice. At the terminal stage of disease, there were no differences in cytokine levels in the tissues of infected WT and caspase-12-/- mice. However, liver pathology was more severe in infected caspase-12-/- mice compared to infected WT mice. Together, these findings indicate that although caspase-12 deficiency results in enhanced pro-inflammatory and immunoregulatory cytokine levels in sera during P. yoelii 17XL infection, these responses are not essential for protection against lethal malaria infection.
为了研究半胱天冬酶-12 缺陷对 IFN-γ 非依赖性控制血期疟原虫的影响，我们比较了野生型 C57BL ⁄ 6J 和 caspase-12-/-小鼠中致死性 Plasmodium yoelii 17XL 感染。感染 caspase-12-/-小鼠在接种后第 8 天和第 9 天的寄生虫血症高于 WT 小鼠，但所有 WT 和 caspase-12-/-小鼠都在第 10 天死亡。此外，与感染 WT 小鼠相比，感染 caspase-12-/-小鼠的血清中 IFN-γ、TNF、IL-18 和 IL-10 水平显著升高。在疾病的终末期，感染 WT 和 caspase-12-/-小鼠组织中的细胞因子水平没有差异。然而，与感染 WT 小鼠相比，感染 caspase-12-/-小鼠的肝脏病理更严重。综上所述，这些发现表明，尽管 caspase-12 缺陷导致 Plasmodium yoelii 17XL 感染期间血清中促炎和免疫调节细胞因子水平升高，但这些反应对预防致死性疟疾感染并非必需。
