Oxidative modification enhances the immunostimulatory effects of extracellular mitochondrial DNA on plasmacytoid dendritic cells

We examined the impact of native and oxidatively modified mitochondrial DNA on the phenotypic and functional properties of plasmacytoid dendritic cells, which possess a fundamental role in the regulation of inflammation and T cell immunity

Kitti Pazmandi; Zsofia Agod; Brahma V. Kumar; Attila Szabo; Tunde Fekete; Viktoria Sogor; Agota Veres; Istvan Boldogh; Eva Rajnavolgyi; Arpad Lanyi; Attila Bacsi

2014

Scholarcy highlights

  • Mitochondria have crucial role in many cellular processes, including ATP, fatty acid and steroid hormone synthesis, the maintenance of Ca2+ homeostasis, thermogenesis and generation of reactive oxygen species
  • The results showed that pre-treatment of the cells with the Toll-like receptor 9 antagonist, prevented the above described phenotypic changes on plasmacytoid dendritic cells, independently from the state of oxidation of mitochondrial DNA
  • Plasma level of mtDNA is elevated during severe sepsis and traumatic injury; it is associated with injury severity and predicts the risk of post-traumatic systemic inflammatory response syndrome
  • Circulating mtDNA can activate human neutrophils through TLR9, leading to their migration and degranulation. These data indicate that extracellular mtDNA acting as a damage-associated molecular pattern can contribute to innate immune responses
  • As mtDNA can be released from various cell types during infections or under inflammatory conditions closely associated with oxidative stress, in this work we examined the immunostimulatory properties of oxidatively damaged mtDNA on pDCs, which exert a crucial role in the regulation of inflammation and T cell immunity
  • Further studies are needed to reveal the clinical significance of our observations, our data indicate that a positive correlation between the 8-oxoG level in extracellular mtDNA and the severity of clinical symptoms may exist in those diseases in which activation of pDCs and/or other Toll-like receptor-9-expressing cells has pivotal role in the pathogenesis

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