Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, New York, United States of America.
PLoS One. 2010 May 3;5(5):e10413. doi: 10.1371/journal.pone.0010413.
Cerebral malaria continues to be a difficult to treat complication of Plasmodium falciparum infection in children. We have shown that platelets can have major deleterious immune functions in experimental cerebral malaria (ECM). One of the platelet derived mediators we have identified as particularly important is platelet factor 4/CXCL4. Our prior work demonstrated that PF4(-/-) mice are protected from ECM, have reduced plasma cytokines, and have reduced T-cell trafficking to the brain. We now show that PF4 drives monocyte cytokine production in a Kruppel like factor 4 (KLF4) dependent manner. Monocyte depleted Plasmodium berghei infected mice have improved survival, and KLF4 is greatly increased in control, but not monocyte depleted mice. PF4(-/-) mice have less cerebral monocyte trafficking and no change in KLF4 expression. These data indicate that PF4 induction of monocyte KLF4 expression may be an important step in the pathogenesis of ECM.
脑型疟疾仍然是儿童中恶性疟原虫感染难以治疗的并发症。我们已经表明，血小板在实验性脑型疟疾（ECM）中具有重要的有害免疫功能。我们已经确定的血小板衍生介质之一是血小板因子 4/CXCL4。我们之前的工作表明，PF4（-/-）小鼠对 ECM 具有保护作用，其血浆细胞因子减少，并且 T 细胞向大脑的迁移减少。现在我们表明，PF4 以依赖于 Kruppel 样因子 4（KLF4）的方式驱动单核细胞细胞因子的产生。单核细胞耗竭的伯氏疟原虫感染小鼠的存活率提高，而控制组但不是单核细胞耗竭的小鼠中 KLF4 大大增加。PF4（-/-）小鼠的脑单核细胞迁移减少，KLF4 表达无变化。这些数据表明，PF4 诱导单核细胞 KLF4 表达可能是 ECM 发病机制中的重要步骤。
