Brucella induced upregulation of NO promote macrophages glycolysis through the NF-κB/G6PD pathway

Int Immunopharmacol. 2024 Dec 5;142(Pt A):113038. doi: 10.1016/j.intimp.2024.113038. Epub 2024 Sep 13.

Abstract

Increased glycolytic metabolism recently emerged as an essential process driving host defense against Brucella, but little is known about how this process is regulated during infection. We have identified a critical role for nuclear factor kappa B (NF-κB) transcription factor regulation in glycolytic switching during Brucella infection for the first time. Chromatin immunoprecipitation with next-generation sequencing for NF-κB and DNA Pull-Down revealed two novel NF-κB-binding sites in the enhancer region of the Nitric oxide (NO)production-response regulator gene glucose-6-phosphate dehydrogenase (G6PD), which is important for the switch to glycolysis during a Brucella infection. These findings demonstrate that Brucella drives metabolic reprogramming by inhibiting host oxidative phosphorylation (OXPHOS) and enhancing its glycolysis via the NF-κB-G6PD-NO-pathway. These studies provide a theoretical basis for investigating drugs or vaccines to control Brucella colonization and induction of undulant by manipulating host metabolic patterns.

Keywords: Brucella; G6PD; Glycolysis; Nitric oxide.

MeSH terms

  • Animals
  • Brucella / immunology
  • Brucellosis* / immunology
  • Brucellosis* / metabolism
  • Glucosephosphate Dehydrogenase* / genetics
  • Glucosephosphate Dehydrogenase* / metabolism
  • Glycolysis*
  • HEK293 Cells
  • Humans
  • Macrophages* / immunology
  • Macrophages* / metabolism
  • Macrophages* / microbiology
  • Mice
  • NF-kappa B* / metabolism
  • Nitric Oxide* / metabolism
  • RAW 264.7 Cells
  • Signal Transduction
  • Up-Regulation

Substances

  • Glucosephosphate Dehydrogenase
  • NF-kappa B
  • Nitric Oxide
  • G6PD protein, human
  • G6pd protein, mouse