Modulation of inflammation and disease tolerance by DNA damage response pathways

FEBS J. 2017 Mar;284(5):680-698. doi: 10.1111/febs.13910. Epub 2016 Oct 26.

Abstract

The accurate replication and repair of DNA is central to organismal survival. This process is challenged by the many factors that can change genetic information such as replication errors and direct damage to the DNA molecule by chemical and physical agents. DNA damage can also result from microorganism invasion as an integral step of their life cycle or as collateral damage from host defense mechanisms against pathogens. Here we review the complex crosstalk of DNA damage response and immune response pathways that might be evolutionarily connected and argue that DNA damage response pathways can be explored therapeutically to induce disease tolerance through the activation of tissue damage control processes. Such approach may constitute the missing pillar in the treatment of critical illnesses caused by multiple organ failure, such as sepsis and septic shock.

Keywords: DNA damage response; disease tolerance; inflammation.

Publication types

  • Review

MeSH terms

  • DNA Damage / genetics*
  • DNA Repair / genetics
  • DNA Replication / genetics
  • Humans
  • Immune Tolerance / genetics
  • Inflammation / genetics
  • Inflammation / immunology*
  • Inflammation / pathology
  • Multiple Organ Failure / genetics
  • Multiple Organ Failure / immunology
  • Multiple Organ Failure / pathology
  • Sepsis / genetics*
  • Sepsis / immunology
  • Sepsis / pathology
  • Shock, Septic / genetics*
  • Shock, Septic / immunology
  • Shock, Septic / pathology
  • Signal Transduction