Olfactory plays a key role in spatiotemporal pathogenesis of cerebral malaria.
Olfactory plays a key role in spatiotemporal pathogenesis of cerebral malaria.
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DOI：
10.1016/j.chom.2014.04.008
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发表时间：
2014-05
影响因子：
30.3
通讯作者：
Hong Zhao;T. Aoshi;S. Kawai;Y. Mori;Aki Konishi;Muge Ozkan;Yukiko Fujita;Yasunari Haseda;M. Shimizu;M. Kohyama;K. Kobiyama;Kei Eto;J. Nabekura;T. Horii;Tomoko Ishino;M. Yuda;H. Hemmi;T. Kaisho;S. Akira;M. Kinoshita;K. Tohyama;Y. Yoshioka;K. Ishii;C. Coban
中科院分区：
文献类型：
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作者：
Hong Zhao;T. Aoshi;S. Kawai;Y. Mori;Aki Konishi;Muge Ozkan;Yukiko Fujita;Yasunari Haseda;M. Shimizu;M. Kohyama;K. Kobiyama;Kei Eto;J. Nabekura;T. Horii;Tomoko Ishino;M. Yuda;H. Hemmi;T. Kaisho;S. Akira;M. Kinoshita;K. Tohyama;Y. Yoshioka;K. Ishii;C. Coban
脑型疟疾是恶性疟原虫感染的一种并发症，以突然昏迷、死亡或神经功能障碍为特征。使用实验性脑型疟疾（ECM）小鼠模型的研究表明，血脑屏障破坏和CD8 T细胞募集有助于疾病，但时空机制知之甚少。我们通过超高场MRI和多光子显微镜显示，嗅球在ECM期间被疟原虫在物理和功能上损坏（嗅觉丧失）。构成嗅球的小梁小毛细血管显示寄生虫积聚和细胞闭塞，随后是微出血，与高热和细胞因子风暴相关的事件。具体而言，嗅觉上调趋化因子CCL21，其受体CCR7和CXCR3的丧失或功能阻断分别导致CD8 T细胞活化和募集减少，以及存活延长。因此，早期检测嗅觉丧失和阻断病理性细胞募集可能为ECM提供潜在的治疗策略。
Cerebral malaria is a complication ofPlasmodium falciparuminfection characterized by sudden coma, death, or neurodisability. Studies using a mouse model of experimental cerebral malaria (ECM) have indicated that blood-brain barrier disruption and CD8 T cell recruitment contribute to disease, but the spatiotemporal mechanisms are poorly understood. We show by ultra-high-field MRI and multiphoton microscopy that the olfactory bulb is physically and functionally damaged (loss of smell) byPlasmodiumparasites during ECM. The trabecular small capillaries comprising the olfactory bulb show parasite accumulation and cell occlusion followed by microbleeding, events associated with high fever and cytokine storm. Specifically, the olfactory upregulates chemokine CCL21, and loss or functional blockade of its receptors CCR7 and CXCR3 results in decreased CD8 T cell activation and recruitment, respectively, as well as prolonged survival. Thus, early detection of olfaction loss and blockade of pathological cell recruitment may offer potential therapeutic strategies for ECM.