Aerobic glycolysis of bronchial epithelial cells rewires Mycoplasma pneumoniae pneumonia and promotes bacterial elimination

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Abstract
The immune response to Mycoplasma pneumoniae infection plays a key role in clinical symptoms. Previous investigations focused on the pro-inflammatory effects of leukocytes and the pivotal role of epithelial cell metabolic status in finely modulating the inflammatory response have been neglected. Herein, we examined how glycolysis in airway epithelial cells is affected by M. pneumoniae infection in an in vitro model. Additionally, we investigated the contribution of ATP to pulmonary inflammation. Metabolic analysis revealed a marked metabolic shift in bronchial epithelial cells during M. pneumoniae infection, characterized by increased glucose uptake, enhanced aerobic glycolysis, and augmented ATP synthesis. Notably, these metabolic alterations are orchestrated by adaptor proteins, MyD88 and TRAM. The resulting synthesized ATP is released into the extracellular milieu via vesicular exocytosis and pannexin protein channels, leading to a substantial increase in extracellular ATP levels. The conditioned medium supernatant from M. pneumoniae -infected epithelial cells enhances the secretion of both interleukin (IL)-1β and IL-18 by peripheral blood mononuclear cells, partially mediated by the P2X7 purine receptor (P2X7R). In vivo experiments confirm that addition of a conditioned medium exacerbates pulmonary inflammation, which can be attenuated by pre-treatment with a P2X7R inhibitor. Collectively, these findings highlight the significance of airway epithelial aerobic glycolysis in enhancing the pulmonary inflammatory response and aiding pathogen clearance.
Funding Information
  • MOST | National Natural Science Foundation of China (81902077, 82101869)
  • Natural Science Foundation of Hunan Province, China (2022JJ30488, 2022JJ40406)
  • Hunan Province Science and Technology Innovation Plant Project (2021SK51906)
  • Scientific Research Project of Hunan Provincial Health Commitee (20201915)
  • Research Foundation of Education Bureau of Hunan Province (20B498)
  • Graduate student scientific research innovation projects in Hunan province (CX20200958, CX202211004)
  • Technology Innovation Project Plan of Health System of Shanghai Putuo District (ptkwws202314)
  • Research Project Plan of the People's Hospital of Putuo District, Shanghai (2022rmky02)
  • Hengyang Science and Technology Planning Project (202250045307)
  • the Emergency special project of epidemic prevention and control of COVID-19 pneumonia in the Unoversity of South China (NO.12)

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