Recognition of Endogenous Nucleic Acids by the Innate Immune System.
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.
Institute for Immunology, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, 01069 Dresden, Germany.
Axel
A
Roers
Institute of Molecular Medicine, University Hospital Bonn, 53127 Bonn, Germany.
Björn
B
Hiller
Institute of Molecular Medicine, University Hospital Bonn, 53127 Bonn, Germany; Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, 81377 Munich, Germany; Center for Integrated Protein Science Munich, 81377 Munich, Germany. Electronic address: hornung@genzentrum.lmu.de.
Veit
V
Hornung
D004247:DNA / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D012313:RNA / Q000276:immunology*; D051192:Receptors, Pattern Recognition / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology
D051192:Receptors, Pattern Recognition; D012313:RNA; D004247:DNA