Inhibition of Glycolysis Impairs Retinoic Acid-Inducible Gene I–Mediated Antiviral Responses in Primary Human Dendritic Cells

• DOI: 10.3389/fcimb.2022.910864
• Publication Date: 2022-07-18T04:34:12Z
• Authors: Alessandra Zevini; Enrico Palermo; Daniele Di Carlo; Magdalini Alexand...; Serena Rinaldo; Alessio Paone; Francesca Cutruzzola; Marilena P. Etna; Eliana M. Coccia; David Olagnier; John Hiscott
• Keywords: 0301 basic medicine; immunometabolism; Tretinoin; Dendritic Cells; METABOLISM; glycolysis; RIG-I; glycolysis; immunometabolism; innate immunity; moDC; viral infection; glycolysis; humans; monocytes; tretinoin; antiviral agents; dendritic cells; Microbiology; Antiviral Agents; QR1-502; Monocytes; moDC; 3. Good health; ACTIVATION; RIG-I; 03 medical and health sciences; Cellular and Infection Microbiology; Humans; SUPPORTS; viral infection; ITACONATE; innate immunity; Glycolysis

Dendritic cells (DCs) are important mediators of the induction and regulation adaptive immune responses following microbial infection inflammation. Sensing environmental danger signals including viruses, products, or inflammatory stimuli by DCs leads to rapid transition from a resting state an activated mature state. DC maturation involves enhanced capturing processing antigens for presentation major histocompatibility complex (MHC) class I II, upregulation chemokines their receptors, cytokines costimulatory molecules, migration lymphoid tissues where they prime naive T cells. Orchestrating cellular response threats requires high bioenergetic cost that accompanies metabolic reprogramming during activation. We previously demonstrated undergo striking functional after stimulation retinoic acid-inducible gene (RIG-I) pathway with synthetic 5′ triphosphate containing RNA (termed M8), consisting interferon (IFN)–stimulated antiviral genes, increased phagocytosis, activation proinflammatory phenotype, markers associated immunogenic cell death. In present study, we set out determine changes RIG-I M8. The rate glycolysis in primary human was activation, glycolytic essential requirement Pharmacological inhibition monocyte-derived dendritic (MoDCs) impaired type IFN signaling disrupting TBK1-IRF3-STAT1 axis, thereby countering activity induced Functionally, resulted viral replication dengue, coronavirus 229E, Coxsackie B5.