Modulation of inflammation and disease tolerance by DNA damage response pathways
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Updated: Mar 14, 2026
Stimulation of Cytoplasmic DNA Sensing Pathways In Vitro and In Vivo
Published on: September 18, 2014
Ana Neves-Costa1, Luis F Moita1
1Instituto Gulbenkian de Ciência, Oeiras, Portugal.
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.
Insights
DNA damage response pathways are crucial for survival and can be therapeutically targeted. Activating these pathways may induce disease tolerance, offering a new treatment for critical illnesses like sepsis.
Area of Science:
- Molecular Biology
- Immunology
- Genetics
Background:
- Accurate DNA replication and repair are vital for organismal survival.
- DNA integrity is threatened by replication errors, chemical/physical agents, and microbial invasion.
- DNA damage can arise from pathogens or host immune responses.
Purpose of the Study:
- To review the interplay between DNA damage response (DDR) and immune response pathways.
- To explore the therapeutic potential of DDR pathways in disease tolerance and critical illness treatment.
Main Methods:
- Literature review of existing research on DDR and immune responses.
- Analysis of evolutionary connections between these pathways.
- Conceptual framework for therapeutic targeting of DDR.
Main Results:
- DDR and immune response pathways exhibit complex crosstalk.
- These pathways may share evolutionary origins.
- DDR activation can potentially induce disease tolerance.
Conclusions:
- Targeting DDR pathways offers a novel therapeutic strategy.
- This approach could be key in treating critical illnesses like sepsis and septic shock.
- Activating tissue damage control via DDR may improve outcomes in multiple organ failure.
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