Innate recognition of non-self nucleic acids

Abstract

The immune system has evolved a plethora of innate receptors that detect microbial DNA and RNA, including Toll-like receptors in the endosomal compartment and RIG-I-like receptors and Nod-like receptors in the cytosol. Here we discuss the recognition of and responses to non-self nucleic acids via these receptors as well as their involvement in autoimmune diseases.

Figure 1

Recognition of microbial RNA and DNA by endosomal Toll-like receptors (TLRs). TLR9, TLR7 (and TLR8), and TLR3 recognize CpG DNA, single-stranded RNA (ssRNA), and double-stranded RNA (dsRNA), respectively. TLR9 and TLR7/8 signal through a Toll-interleukin-1 receptor- (TIR-) containing adaptor molecule MyD88, whereas TLR3 signals exclusively through a different adaptor, TRIF. MyD88 and TRIF induce the expression of genes for type I interferons and pro-inflammatory cytokines by activating transcription factors of the IRF and NFκB families. DD, death domain; IRF, interferon response factor; LRR, leucine-rich repeat; NF, nuclear factor; SHIM, RIP homotypic interaction motif.

Figure 2

Recognition of microbial RNA and DNA by cytoplasmic pattern recognition receptors. RIG-I and MDA5 recognize 5'-triphosphate ssRNA and dsRNA from RNA viruses and trigger signaling cascades via a CARD-containing adaptor molecule, IPS-1. IPS-1 induces the expression of genes for type I interferons and pro-inflammatory cytokines by activating transcription factors of the IRF and NFκB families. The role of LGP2 in RNA virus recognition is unclear and LGP2 has been proposed to inhibit RIG-I activity. DAI recognizes dsDNA and induces gene expression through an unknown adaptor molecule. Modular structures of the receptor proteins are shown with the abbreviations of the domains as follows: CARD, caspase activating recruitment domains; helicase, RNA-binding domain; RD, repressor domain; TM, transmembrane domain; Zα and Zβ, Z-DNA binding domain α and β; D3, tentative name for an additional DNA-binding region; SD, signaling domain.