title: Induction of type I IFNs by intracellular DNA-sensing pathways.
abstract: A successful antimicrobial immune response involves the coordinate action of cells and soluble factors, with the cytokine family of type I interferons (IFNs) having a central role. Type I IFNs are not only crucial in conferring immediate antimicrobial, most importantly antiviral effects, but they also have an essential role in bridging the innate with the adaptive immune response. Therefore, production of these key cytokines must be tightly controlled. To this effect the host has evolved a set of pattern recognition receptors (PRRs) that reliably and specifically detect the presence of microbial pathogens before mounting an IFN response. Most PRR pathways that are known to induce type I IFNs are triggered upon recognition of nucleic acids. This mode of sensing is not straightforward, as large amounts of RNA and DNA are also present within the host. Nevertheless, in some cases distinct molecular features that are present within foreign nucleic acids but absent in endogenous nucleic acids, allow the host to reliably discriminate between 'self' and 'non-self'. At the same time, compartmentalization of PRRs within subcellular organelles that are usually devoid of host nucleic acids, but are sites of pathogen localization, is another principle that enables the host to distinguish self from non-self. The latter mode of sensing applies to the detection of microbial DNA within the cytoplasm, a compartment in which host DNAs are usually not present. Despite the past years' tremendous progress in the field of innate immunity, our understanding of cytoplasmic DNA sensing mechanisms is only beginning to form/take form. In this review, we outline the recent advancements in the elucidation of intracellular DNA-sensing pathways and discuss the future directions of this emerging field.
authors.affiliation: Institute for Clinical Chemistry and Clinical Pharmacology, Unit for Clinical Biochemistry, University Hospital, University of Bonn, Bonn, Germany.
authors.forename: Taner
authors.initials: T
authors.lastname: Cavlar
authors.forename: Andrea
authors.initials: A
authors.lastname: Ablasser
authors.forename: Veit
authors.initials: V
authors.lastname: Hornung
mesh_terms: D000818:Animals; D002450:Cell Communication; D004247:DNA / Q000276:immunology*; D006801:Humans; D007370:Interferon Type I / Q000276:immunology*; D042541:Intracellular Space / Q000276:immunology; D051192:Receptors, Pattern Recognition / Q000276:immunology*; D017634:Self Tolerance; D015398:Signal Transduction / Q000276:immunology
chemical_list: D007370:Interferon Type I; D051192:Receptors, Pattern Recognition; D004247:DNA