Metabolic Programming Drives Protective and Inflammatory Monocyte Fates in Viral Encephalitis.

ABSTRACT: Infiltrating monocytes can exert both protective and pathogenic effects during central nervous system (CNS) inflammation. However, the metabolic mechanisms that govern these divergent roles remain poorly understood, limiting opportunities for therapeutic intervention. Single-cell RNA-sequencing and metabolic flow analysis of brain and bone marrow (BM) is used to map the metabolic signatures of monocyte-derived cells (MCs) during lethal West Nile virus encephalitis. Trajectory analysis shows that BM monocytes progress through three metabolic profiles before migrating to the brain and differentiating into a pro-inflammatory HIF1-α⁺ MC population. This population further diverges into an inflammatory, iNOS⁺ MC subset with high glycolysis and amino acid metabolism, and a protective, glycolytic

SUBMITTER: Wishart CL 

PROVIDER: S-EPMC12412471 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature