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Sensing Self and Non-Self DNA by Innate Immune Receptors and Their Signaling Pathways

Sophia P M Sok1, Daisuke Ori2, Noor Hasima Nagoor3

  • 1Laboratory of Molecular Immunobiology, Division of Biological Science, Graduate School of Science and Technology, Nara Institute of Science and Technology (NAIST), Nara, Japan; Institute of Postgraduate Studies (IPS), University of Malaya, 50603 Kuala Lumpur, Malaysia; Centre of Research in Biotechnology for Agriculture (CEBAR), University of Malaya, 50603 Kuala Lumpur, Malaysia.

Critical Reviews in Immunology
|February 27, 2019
PubMed

Insights

The innate immune system uses DNA sensors to detect pathogens and cell damage, triggering crucial immune responses. Dysregulation of these DNA signaling pathways can lead to autoimmune diseases and cancer.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • The innate immune system is the host's primary defense against pathogens.
  • Pattern recognition receptors (PRRs) detect pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), including self and non-self DNA.
  • Sensing DNA initiates innate immune responses via type I interferons (IFNs) and proinflammatory cytokines, involving key regulators like interferon regulatory factor 3 (IRF3) and nuclear factor kappa B (NF-κB).

Purpose of the Study:

  • To provide an updated overview of DNA signaling pathways in innate immunity.
  • To highlight the roles of DNA sensing in host defense against pathogens and in response to cell injury.
  • To discuss the implications of DNA sensor dysregulation in autoimmune diseases and cancer, and pathogen evasion strategies.

Main Methods:

  • Review of current literature on DNA sensing pathways.
  • Analysis of signaling cascades involving PRRs, IRF3, and NF-κB.
  • Discussion of immune homeostasis and host defense mechanisms.

Main Results:

  • DNA sensing by PRRs is critical for initiating innate immune responses, including IFN and cytokine production.
  • Activation of IRF3 and NF-κB are central to these signaling pathways.
  • Defects in DNA sensing and signaling contribute to immune dysregulation, autoimmunity, and cancer.

Conclusions:

  • DNA signaling pathways are fundamental to innate immunity, linking it with adaptive immunity.
  • Proper regulation of DNA sensors is essential for maintaining host homeostasis and preventing disease.
  • Understanding these pathways offers insights into therapeutic strategies against infections, autoimmune disorders, and cancer.

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