Dataset Information

Dysregulation of macrophage lipid metabolism underlies intracellular bacterial neuroinvasion

ABSTRACT: Acute infection of the central nervous system is one of the deadliest diseases, but the mechanisms by which intracellular bacteria infiltrate the brain remain poorly understood. 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. Taken together, our findings uncover a pathway by which intracellular bacteria hijack macrophages to invade the brain, suggesting that lipid metabolism might play a role in the prevention or resolution of bacterial neuroinvasion.

ORGANISM(S): Mus musculus

PROVIDER: GSE264020 | GEO | 2026/03/17

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Atherosclerosis-associated vascular disease is the leading cause of death worldwide. Clinical and experimental data demonstrated that circulating monocytes internalize plasma lipoproteins and become lipid-laden foamy cells in hypercholesterolemic subjects. This study was designed to identify the endocytic mechanisms responsible for foamy monocyte formation, perform functional and transcriptomic analysis of foamy and non-foamy monocytes, and characterize specific monocyte subsets in the circulation from normocholesterolemic controls and hypercholesterolemic patients. The presence of foamy monocytes was confirmed in hypercholesterolemic mice and humans via flow cytometry analysis. High resolution scanning electron microscopy (SEM) and quantification of FITC/TRITC-dextran internalization demonstrated macropinocytosis stimulation in human (THP-1) and wild type murine monocytes in vitro. Stimulation of macropinocytosis induced foamy monocyte formation in the presence of unmodified, native LDL (nLDL) and oxidized LDL (ox-LDL) in vitro. Genetic blockade of macropinocytosis (LysMCre+ Nhe1f/f) inhibited foamy monocyte formation in hypercholesterolemic mice in vivo and attenuated monocyte adhesion to atherosclerotic aortas ex vivo. qRT-PCR quantified mRNA levels of major scavenger receptors (SR) in foamy and non-foamy monocytes and identified CD36 as a major SR increasing in response to lipid loading. Deletion of CD36 (Cd36-/-) inhibited foamy monocyte formation in hypercholesterolemic mice. Mechanistic studies identified NADPH oxidase 2 (Nox2)-derived superoxide (O2⋅−) as an important downstream signaling molecule stimulating macropinocytosis in monocytes. Bulk RNA-sequencing characterized transcriptional differences between non-foamy and foamy monocytes and macrophages. Flow cytometry analysis of CD14 and CD16 expression demonstrated a significant increase in intermediate monocytes in hypercholesterolemic patients compared to normocholesterolemic controls. These results provide novel insights into the mechanisms of foamy monocyte formation and potentially identify new therapeutic targets in the treatment of atherosclerosis.

Dataset Information

Dysregulation of macrophage lipid metabolism underlies intracellular bacterial neuroinvasion

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets