Low Density Lipoprotein Exposure of Plasmacytoid Dendritic Cells Blunts Toll-like Receptor 7/9 Signaling via NUR77

Anette Christ, Pieter G Goossens, Erwin Wijnands, Han Jin, Bart Legein, Tammy Oth, Aaron Isaacs, Monika Stoll, Joris Vanderlocht, Esther Lutgens, Mat J A P Daemen, Martin Zenke, Erik A L Biessen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

BACKGROUND: Pathogens or trauma-derived danger signals induced maturation and activation of plasmacytoid dendritic cells (pDCs) is a pivotal step in pDC-dependent host defense. Exposure of pDC to cardiometabolic disease-associated lipids and proteins may well influence critical signaling pathways, thereby compromising immune responses against endogenous, bacterial and viral pathogens. In this study, we have addressed if hyperlipidemia impacts human pDC activation, cytokine response and capacity to prime CD4+ T cells.

METHODS AND RESULTS: We show that exposure to pro-atherogenic oxidized low-density lipoproteins (oxLDL) led to pDC lipid accumulation, which in turn ablated a Toll-like receptor (TLR) 7 and 9 dependent up-regulation of pDC maturation markers CD40, CD83, CD86 and HLA-DR. Moreover, oxLDL dampened TLR9 activation induced the production of pro-inflammatory cytokines in a NUR77/IRF7 dependent manner and impaired the capacity of pDCs to prime and polarize CD4+ T helper (Th) cells.

CONCLUSION: Our findings reveal profound effects of dyslipidemia on pDC responses to pathogen-derived signals.

Original languageEnglish
Article number1152
Number of pages17
JournalBiomedicines
Volume10
Issue number5
DOIs
Publication statusPublished - 17 May 2022

Keywords

  • ANTIGEN PRESENTATION
  • ATHEROSCLEROTIC LESIONS
  • CHEMOKINES
  • DISEASE
  • INTERFERON-PRODUCING CELLS
  • MATURATION
  • MICE
  • MIGRATION
  • VIRUS
  • cholesterol
  • dendritic cells
  • interferon
  • nuclear receptor
  • toll like receptors
  • viral response

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