Adderley Jack D, Doerig Christian
Centre for Chronic Infectious and Inflammation Disease, Biomedical Sciences Cluster, School of Health and Biomedical Sciences, RMIT University, Bundoora VIC 3083, Australia.
Microb Cell. 2020 Sep 16;7(10):286-288. doi: 10.15698/mic2020.10.733.
It is well established that intracellular pathogens mobilise signalling pathways to manipulate gene expression of their host cell to promote their own survival. Surprisingly, there is evidence that specific host signalling molecules are likewise activated in a-nucleated erythrocytes in response to infection with malaria parasites. In this paper (Adderley , Nature Communications 2020), we report the system-wide assessment of host erythrocyte signalling during the course of infection with . This was achieved through the use of antibody microarrays containing >800 antibodies directed against human signalling proteins, which enabled us to interrogate the status of host erythrocyte signalling pathways at the ring, trophozoite and schizont stages of parasite development. This not only confirmed the pre-existing fragmentary data on the activation of a host erythrocyte PAK-MEK pathway, but also identified dynamic changes to many additional signalling elements, with trophozoite-infected erythrocytes displaying the largest mobilisation of host cell signalling. This study generated a comprehensive dataset on the modulation of host erythrocyte signalling during infection with , and provides the proof of principle that human protein kinases activated by infection represent attractive targets for antimalarial intervention.
众所周知，细胞内病原体可调动信号通路来操纵宿主细胞的基因表达，以促进自身存活。令人惊讶的是，有证据表明，在感染疟原虫后，特定的宿主信号分子同样会在无核红细胞中被激活。在本文（阿德利，《自然通讯》2020年）中，我们报告了在感染 过程中对宿主红细胞信号进行全系统评估的情况。这是通过使用含有800多种针对人类信号蛋白的抗体的抗体微阵列实现的，这使我们能够在寄生虫发育的环状体、滋养体和裂殖体阶段询问宿主红细胞信号通路的状态。这不仅证实了关于宿主红细胞PAK - MEK通路激活的先前零碎数据，还确定了许多其他信号元件的动态变化，其中感染滋养体的红细胞显示出宿主细胞信号的最大调动。这项研究生成了关于感染 期间宿主红细胞信号调节的全面数据集，并提供了原理证明，即由 感染激活的人类蛋白激酶是抗疟干预的有吸引力的靶点。
