Nucleic Acid Recognition by the Innate Immune System

Abstract

Receptors of the innate immune system recognize conserved microbial features and provide key signals that initiate immune responses. Multiple transmembrane and cytosolic receptors have evolved to recognize RNA and DNA, including members of the Toll-like receptor and RIG-I-like receptor families and several DNA sensors. This strategy enables recognition of a broad range of pathogens; however, in some cases, this benefit is weighed against the cost of potential self recognition. Recognition of self nucleic acids by the innate immune system contributes to the pathology associated with several autoimmune or autoinflammatory diseases. In this review, we highlight our current understanding of nucleic acid sensing by innate immune receptors and discuss the regulatory mechanisms that normally prevent inappropriate responses to self.

Toll-like receptors, signaling adapters and regulation of the pro-inflammatory response by PI3K

“…[42][43][44][45] Activation of ERK1/2 proceeds TBK1 and IKKε then mediate phosphorylation of IRF3. 55,56 Consequently, cells deficient in TRAF3, TBK1 or IKKε are severely compromised in their ability to activate IRF3 and induce IFNβ upon TLR3 stimulation. 53,[55][56][57][58] PI3K.…”

“…55,56 Consequently, cells deficient in TRAF3, TBK1 or IKKε are severely compromised in their ability to activate IRF3 and induce IFNβ upon TLR3 stimulation. 53,[55][56][57][58] PI3K. Phosphoinositide 3-kinases (PI3K) are a family of lipid kinases consisting of three classes (class I, class II and class III) based upon substrate specificity as well as several structural characteristics.…”

RNA editing by ADAR1 marks dsRNA as “self”

“…Both RIG-I and MDA5 were identified as the major sensors of cytosolic RNA and played crucial roles in dsR-NA-induced innate antiviral responses [9]. However, they preferred different RNA chains.…”

Critical role of Toll-like receptor signaling in NK cell activation

“…These TLRs are roughly divided into two subfamilies depending on their cellular localization and respective PAMP ligands. One group is composed of TLR1, TLR2, TLR4, TLR5, TLR6 and TLR11, which are expressed on cell surface and recognize mainly microbial lipids components such as LPS and lipoproteins; the other group mainly includes TLR3, TLR7, TLR8 and TLR9, which are expressed exclusively in intracellular vesicles such as endoplasmic reticulum (ER), endosomes, lysosomes and endolysosomes, where they recognize microbial nucleic acids components such as double-stranded RNA (dsRNA), single-stranded RNA (ssRNA), unmethylated-CpG DNA motifs respectively [14,15]. So it is essential for these "nucleic acid-sensing" TLRs to internalize to the endosome before signaling is possible.…”