Reprograming of metabolic pathways is critical in governing the polarization of macrophages into classical proinflammatory M1 or alternative anti‐inflammatory M2 phenotypes in metabolic diseases, such as diabetes. Porphyromonas gingivalis, a keystone pathogen of periodontitis, causes an imbalance in M1/M2 activation, resulting in a hyperinflammatory environment that promotes the pathogenesis of periodontitis. However, whether P. gingivalis infection modulates metabolic pathways to alter macrophage polarization remains unclear. Bone‐marrow‐derived macrophages (BMDMs) were collected from 6‐week‐old female C57BL/6 mice and stimulated with P. gingivalis, P. gingivalis‐derived LPS or IL‐4. Relative gene expression and protein production were measured by quantitative real‐time PCR, RNA sequencing and western blotting. Colorimetric assays were also performed to assess the amounts of α‐ketoglutarate (α‐KG) and succinate. P. gingivalis or P. gingivalis‐derived LPS‐induced inflammatory responses enhanced M1 macrophages and suppressed M2 macrophages, even in the presence of IL‐4. P. gingivalis inhibited Idh1/2 and Gpt1/2 mRNA expression, and increased Akgdh mRNA expression, thus decreasing the ratio of α‐KG/succinate. Supplementation of cell‐permeable dimethyl‐α‐KG dramatically restored M2 activation during P. gingivalis infection. Our study suggests that P. gingivalis maintains a hyperinflammatory state by suppressing the production of α‐KG by M2 macrophages.

中文翻译：

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牙龈卟啉单胞菌通过抑制小鼠中α-酮戊二酸的产生来抑制巨噬细胞的M2活化。

代谢途径的重编程对于控制巨噬细胞在代谢性疾病（例如糖尿病）中分化为经典的促炎性M1或其他抗炎性M2表型至关重要。牙周炎的关键病原菌牙龈卟啉单胞菌引起M1 / M2活化失衡，导致过度炎性环境，促进牙周炎的发病机理。然而，牙龈卟啉单胞菌感染是否调节新陈代谢途径以改变巨噬细胞极化仍不清楚。从6周龄雌性C57BL / 6小鼠中收集骨髓源巨噬细胞（BMDM），并用牙龈卟啉单胞菌，牙龈卟啉单胞菌刺激派生的LPS或IL-4。通过定量实时PCR，RNA测序和蛋白质印迹法测量相对基因表达和蛋白质产生。还进行了比色测定，以评估α-酮戊二酸（α-KG）和琥珀酸酯的含量。牙龈卟啉单胞菌或牙龈卟啉单胞菌衍生的LPS诱导的炎症反应增强了M1巨噬细胞并抑制了M2巨噬细胞，即使存在IL-4。牙龈卟啉单胞菌抑制Idh1 / 2和Gpt1 / 2 mRNA表达，并增加Akgdh mRNA表达，从而降低α-KG/琥珀酸酯的比率。补充可渗透细胞的二甲基-α-KG可显着恢复牙龈卟啉单胞菌期间的M2活化感染。我们的研究表明，牙龈卟啉单胞菌通过抑制M2巨噬细胞产生α-KG来维持高炎症状态。