Cited by 543Immune Response and Inflammationinterferon and immune responsesInflammasome and immune disorders

Recognition of Endogenous Nucleic Acids by the Innate Immune System

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Roers, Axel, Hiller, Björn, Hornung, Veit·2016·Immunity

Abstract

Recognition of DNA and RNA by endosomal and cytosolic sensors constitutes a central element in the detection of microbial invaders by the innate immune system. However, the capacity of these sensors to discriminate between microbial and endogenous nucleic acids is limited. Over the past few years, evidence has accumulated to suggest that endogenous DNA or RNA species can engage nucleic-acid-sensing pattern-recognition receptors that can trigger or sustain detrimental pathology. Here, we review principles of how the activation of innate sensors by host nucleic acids is prevented in the steady state and discuss four important determinants of whether a nucleic-acid-driven innate response is mounted. These include structural features of the ligand being sensed, the subcellular location and quantity of pathogen-derived or endogenous nucleic acids, and the regulation of sensor-activation thresholds. Furthermore, we emphasize disease mechanisms initiated by failure to discriminate self from non-self in nucleic acid detection.

Integrity signals

Registry

Crossref · 10.1016/j.immuni.2016.04.002

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162 of 162 references verified0 citation errors · 0 not checkable

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  • DAMPs from senescent, damaged, and dying cells trigger various cell death modalities, including necrosis, pyroptosis, necroptosis, PANoptosis, NETosis, and ferroptosis.

    “In summary, DAMPs from senescent, damaged, and dying cells trigger various cell death modalities, including necrosis, pyroptosis, necroptosis, PANoptosis, NETosis, and ferroptosis (Fig. 4).”
  • DAMPs bind to specific receptors, initiating inflammation and orchestrating a coordinated response involving immune cells.

    “DAMPs bind to specific receptors, initiating inflammation and orchestrating a coordinated response involving immune cells.”
  • This response includes the recruitment of neutrophils and monocytes, which play crucial roles in tissue repair and healing processes.

    “This response includes the recruitment of neutrophils and monocytes, which play crucial roles in tissue repair and healing processes.”
  • Endogenous DAMPs can activate PRRs and non-PRR transmembrane proteins, resulting in massive inflammation, cellular senescence, diseases of the organs, and aging.

    “Endogenous DAMPs can activate PRRs and non-PRR transmembrane proteins, resulting in massive inflammation, cellular senescence, diseases of the organs, and aging.277–279”
  • When leukocytes fail to clear immunostimulatory molecules, inflammation persists, which further causes cancer and aging.

    “When leukocytes fail to clear immunostimulatory molecules, inflammation persists, which further causes cancer and aging.”

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Authors
Roers, A., Hiller, B., & Hornung, V.
Affiliations
  • Technische Universität Dresden (DE)
  • University Hospital Bonn (DE)
  • Center for Integrated Protein Science Munich (DE)
Corresponding author
Hornung, Veit
Venue
Immunity
Publisher
Elsevier BV
Published
2016-04
Volume
44
Issue
4
Pages
739-754
ISSN
1074-7613 (ISSN-L)
OpenAlex
W2340906209
Cited by
541
References
164
Citations by year
2026: 32 · 2025: 42 · 2024: 64 · 2023: 43 · 2022: 57 · 2021: 65 · 2020: 66 · 2019: 72 · 2018: 53 · 2017: 35 · 2016: 12
FWCI
5.53
Type
journal article
Language
en
Open access
Locations
  • Immunity (publishedVersion)
  • PubMed (publishedVersion)
  • MPG.PuRe (Max Planck Society) (submittedVersion)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
Keywords
innate immunity, pattern recognition receptors, autoinflammation, autoimmunity
MeSH terms
DNA, Humans, Immunity, Innate, RNA, Signal Transduction, Receptors, Pattern Recognition

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