PLoS Pathogens (Aug 2022)

Succinate and inosine coordinate innate immune response to bacterial infection.

  • Ming Jiang,
  • Zhuang-Gui Chen,
  • Hui Li,
  • Tian-Tuo Zhang,
  • Man-Jun Yang,
  • Xuan-Xian Peng,
  • Bo Peng

DOI
https://doi.org/10.1371/journal.ppat.1010796
Journal volume & issue
Vol. 18, no. 8
p. e1010796

Abstract

Read online

Macrophages restrict bacterial infection partly by stimulating phagocytosis and partly by stimulating release of cytokines and complement components. Here, we treat macrophages with LPS and a bacterial pathogen, and demonstrate that expression of cytokine IL-1β and bacterial phagocytosis increase to a transient peak 8 to 12 h post-treatment, while expression of complement component 3 (C3) continues to rise for 24 h post-treatment. Metabolomic analysis suggests a correlation between the cellular concentrations of succinate and IL-1β and of inosine and C3. This may involve a regulatory feedback mechanism, whereby succinate stimulates and inosine inhibits HIF-1α through their competitive interactions with prolyl hydroxylase. Furthermore, increased level of inosine in LPS-stimulated macrophages is linked to accumulation of adenosine monophosphate and that exogenous inosine improves the survival of bacterial pathogen-infected mice and tilapia. The implications of these data suggests potential therapeutic tools to prevent, manage or treat bacterial infections.