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<p>Acute central nervous system infection is highly lethal, yet the mechanisms by which intracellular bacteria infiltrate the brain remain unclear. Phagocytes are central to host defense, but how infected cells facilitate bacterial access to the brain is poorly defined. In this study, we characterize a CD36<sup>+</sup> Fabp4<sup>+</sup> Pparg<sup>+</sup> macrophage subset that mediates bacterial penetration of the brain without disrupting the blood–brain barrier. Biomechanical analysis reveals that CD36<sup>+</sup> macrophages exhibit abundant protrusions and adhesion molecules, enabling resistance to blood flow shear stress and promoting endothelial adhesion. Metabolomic profiling reveals dysregulated lipid metabolism during neuroinvasion, with β-hydroxybutyrate promoting the differentiation and survival of CD36<sup>+</sup> macrophages. Importantly, ketogenesis exacerbates symptoms during bacterial neuroinvasion, which could be halted by physiological glucose supplementation. Here, we show that intracellular bacteria exploit metabolically reprogrammed macrophages to access the brain, highlighting glycolipid metabolic homeostasis as a potential therapeutic target in bacterial neuroinvasion.</p>

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Dysregulation of macrophage lipid metabolism underlies intracellular bacterial neuroinvasion

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月14日

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  • Zhou Sha,
  • Kun Yang,
  • Shoupeng Fu,
  • Xiaoyong Tong,
  • Hui Yang,
  • Huiling Fang,
  • Qianqian He,
  • Ning Li,
  • Xinyu Shu,
  • Qi Liu,
  • Beibei Fu,
  • Jin Liu,
  • Qian Li,
  • Hao Zeng,
  • Xiaokai Zhang,
  • Rui Yao,
  • Xushuo Zhang,
  • Wenjin Guo,
  • Xuhu Mao,
  • Mian Long,
  • Xiaoyuan Lin,
  • Quanming Zou,
  • Haibo Wu

摘要

Acute central nervous system infection is highly lethal, yet the mechanisms by which intracellular bacteria infiltrate the brain remain unclear. Phagocytes are central to host defense, but how infected cells facilitate bacterial access to the brain is poorly defined. In this study, we characterize a CD36+ Fabp4+ Pparg+ macrophage subset that mediates bacterial penetration of the brain without disrupting the blood–brain barrier. Biomechanical analysis reveals that CD36+ macrophages exhibit abundant protrusions and adhesion molecules, enabling resistance to blood flow shear stress and promoting endothelial adhesion. Metabolomic profiling reveals dysregulated lipid metabolism during neuroinvasion, with β-hydroxybutyrate promoting the differentiation and survival of CD36+ macrophages. Importantly, ketogenesis exacerbates symptoms during bacterial neuroinvasion, which could be halted by physiological glucose supplementation. Here, we show that intracellular bacteria exploit metabolically reprogrammed macrophages to access the brain, highlighting glycolipid metabolic homeostasis as a potential therapeutic target in bacterial neuroinvasion.