The cecal ligation and perforation (CLP) model is the gold standard for the polymicrobial sepsis. In the CLP mice, the myeloid cells play an important role in septic shock. The phenotypes and the activation state of the macrophage and neutrophil correlate with their metabolism. In the present study, we generated the specific myeloid deletion of PDK1 and mTOR mice, which was the important regulator of metabolic signaling. We found that the deletion of PDK1 in the myeloid cells could aggravate the early septic shock in the CLP mice, as well as the deletion of mTORC1 and mTORC2. Moreover, PDK1 deletion attenuated the inflammation induced by LPS in the late stage on CLP mice, which was exacerbated in mTORC1 and mTORC2 knockout mice. Both PDK1 and mTORC1/2 could not only regulate the cellular metabolism but also play important roles on the myeloid cells in the secondary stimulation of sepsis. The present study will provide a theoretical prospect for the therapy of the septic shock in different stages.

中文翻译：

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髓样细胞中的PDK1 / mTOR信号差异调节败血症的早期和晚期。

盲肠结扎穿孔（CLP）模型是多菌性败血症的金标准。在CLP小鼠中，髓样细胞在败血性休克中起重要作用。巨噬细胞和嗜中性粒细胞的表型和活化状态与其代谢相关。在本研究中，我们产生了PDK1和mTOR小鼠的特定髓样缺失，这是代谢信号的重要调节剂。我们发现，髓样细胞中PDK1的缺失会加重CLP小鼠的早期败血性休克，以及mTORC1和mTORC2的缺失。此外，PDK1缺失减轻了CLP小鼠在后期由LPS诱导的炎症，在mTORC1和mTORC2敲除小鼠中加剧了。PDK1和mTORC1 / 2不仅可以调节细胞的代谢，而且在脓毒症的二次刺激中对髓样细胞也起着重要的作用。本研究将为不同阶段的败血性休克的治疗提供理论依据。