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Recognition of Endogenous Nucleic Acids by the Innate Immune System
Open accessAbstract
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.
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“In summary, DAMPs from senescent, damaged, and dying cells trigger various cell death modalities, including necrosis, pyroptosis, necroptosis, PANoptosis, NETosis, and ferroptosis (Fig. 4).”
From Inflammation and aging: signaling pathways and intervention therapies (2023) · cites this paper as [279]
In the citing paper
“DAMPs bind to specific receptors, initiating inflammation and orchestrating a coordinated response involving immune cells.”
From Inflammation and aging: signaling pathways and intervention therapies (2023) · cites this paper as [279]
In the citing paper
“This response includes the recruitment of neutrophils and monocytes, which play crucial roles in tissue repair and healing processes.”
From Inflammation and aging: signaling pathways and intervention therapies (2023) · cites this paper as [279]
In the citing paper
“Endogenous DAMPs can activate PRRs and non-PRR transmembrane proteins, resulting in massive inflammation, cellular senescence, diseases of the organs, and aging.277–279”
From Inflammation and aging: signaling pathways and intervention therapies (2023) · cites this paper as [279]
In the citing paper
“When leukocytes fail to clear immunostimulatory molecules, inflammation persists, which further causes cancer and aging.”
From Inflammation and aging: signaling pathways and intervention therapies (2023) · cites this paper as [279]
In the citing paper
“These degradation products are presumably produced by nucleases in the endosome shortly after the RNA is internalized (Roers et al. 2016).”
From RNA Circularization Diminishes Immunogenicity and Can Extend Translation Duration In Vivo (2019) · cites this paper as Roers et al. 2016
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Metadata
- 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
- bronze
- doi.org
- Licence
- 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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