Dysregulation of macrophage lipid metabolism underlies intracellular bacterial neuroinvasion

Phagocytic cells are usually recognized as the battlefield on which war is waged against intracellular bacteria; however, little is known about how the intracellular bacteria take advantage of infected phagocytes to access the brain. In this study, we find that a novel CD36+ foamy macrophage subpopulation participates in penetration of the brain by intracellular bacteria.

Biomechanical analysis reveals that abundant protrusions and adhesion molecules on foamy macrophages confer significant resistance to the mechanical stress of blood flow, thereby providing more opportunities for these macrophages to adhere to the vascular endothelial surface during neuroinvasion. Through metabolomics analysis, we find that macrophage lipid metabolism is recalibrated during bacterial neuroinvasion, and that β-hydroxybutyrate promotes the formation and survival of CD36+ foamy macrophages.