Platelet Induction of the Acute-Phase Response Is Protective in Murine Experimental Cerebral Malaria
Platelet Induction of the Acute-Phase Response Is Protective in Murine Experimental Cerebral Malaria
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DOI：
10.4049/jimmunol.1202672
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发表时间：
2013-05-01
影响因子：
4.4
通讯作者：
Morrell, Craig N.
中科院分区：
文献类型：
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作者：
Aggrey, Angela A.;Srivastava, Kalyan;Morrell, Craig N.
血小板最被认为是血栓形成的细胞介质，但它们的免疫调节作用（包括对疟原虫感染的反应）越来越受到重视。血小板与内皮细胞和白细胞的相互作用在实验性脑型疟疾（ECM）的发病机制中发挥着重要作用。最近，有人提出，血小板不仅在脑型疟疾中具有不利作用，而且在无并发症的疟疾动物模型中也可能具有保护作用。我们现在证明，血小板的这些多样化且看似矛盾的作用延伸到脑型疟疾模型，并且取决于感染期间血小板激活的时间。我们的数据表明，血小板在 ECM 中很早就被激活，并且在针对血液阶段感染的急性期反应的启动中发挥着核心作用。与感染后血小板消耗或抑制不同，感染前血小板消耗或血小板抑制剂治疗不具有保护作用。此外，我们发现血小板驱动的急性期反应在通过限制寄生虫生长来保护小鼠免受 ECM 侵害方面发挥着重要作用。我们现在的数据表明，血小板在 ECM 发病机制中发挥着复杂的作用：血小板有助于限制感染后早期寄生虫的生长，但随着疾病的进展，随着血小板的持续激活，血小板会导致 ECM 相关炎症。免疫学杂志，2013，190：4685-4691。
Platelets are most recognized as the cellular mediator of thrombosis, but they are increasingly appreciated for their immunomodulatory roles, including responses to Plasmodium infection. Platelet interactions with endothelial cells and leukocytes contribute significantly to the pathogenesis of experimental cerebral malaria (ECM). Recently, it has been suggested that platelets not only have an adverse role in cerebral malaria, but platelets may also be protective in animal models of uncomplicated malaria. We now demonstrate that these diverse and seemingly contradictory roles for platelets extend to cerebral malaria models and are dependent on the timing of platelet activation during infection. Our data show that platelets are activated very early in ECM and have a central role in initiation of the acute-phase response to blood-stage infection. Unlike platelet depletion or inhibition postinfection, preinfection platelet depletion or treatment with a platelet inhibitor is not protective. Additionally, we show that platelet-driven acute-phase responses have a major role in protecting mice from ECM by limiting parasite growth. Our data now suggest that platelets have a complex role in ECM pathogenesis: platelets help limit parasite growth early postinfection, but with continued platelet activation as the disease progresses, platelets contribute to ECM-associated inflammation. The Journal of Immunology, 2013, 190: 4685-4691.