Glutathione Metabolism Contributes to the Induction of Trained Immunity

Cells

JuanCarlos Alarcon-Barrera¹  Sarantos Kostidis¹  MartinA. Giera¹  ValerieA.C.M. Koeken²  MihaiG. Netea²  SimoneJ.C.F.M. Moorlag²  Jorge Domínguez-Andrés²  AnaisaV. Ferreira²  Vasiliki Matzaraki²  L.Charlotte J. de Bree²  VeraP. Mourits²  Boris Novakovic³ 

[1] Center for Proteomics and Metabolomics, Leiden University Medical Center (LUMC), 2333 ZA Leiden, The Netherlands;Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Nijmegen Medical Center, 6500HB Nijmegen, The Netherlands;Epigenetics Research, Murdoch Children’s Research Institute, Parkville, VIC 3052, Australia;

关键词: glutathione;    trained immunity;    macrophages;    metabolism;    innate immune memory;   

DOI  :  10.3390/cells10050971

来源: DOAJ

【 摘 要 】

The innate immune system displays heterologous memory characteristics, which are characterized by stronger responses to a secondary challenge. This phenomenon termed trained immunity relies on epigenetic and metabolic rewiring of innate immune cells. As reactive oxygen species (ROS) production has been associated with the trained immunity phenotype, we hypothesized that the increased ROS levels and the main intracellular redox molecule glutathione play a role in the induction of trained immunity. Here we show that pharmacological inhibition of ROS in an in vitro model of trained immunity did not influence cell responsiveness; the modulation of glutathione levels reduced pro-inflammatory cytokine production in human monocytes. Single nucleotide polymorphisms (SNPs) in genes involved in glutathione metabolism were found to be associated with changes in pro-inflammatory cytokine production capacity upon trained immunity. Also, plasma glutathione concentrations were positively associated with ex vivo IL-1β production, a biomarker of trained immunity, produced by monocytes of BCG-vaccinated individuals. In conclusion, glutathione metabolism is involved in the induction of trained immunity, and future studies are warranted to explore its functional consequences in human diseases.

【 授权许可】

Unknown