RNA recognition via TLR7 and TLR8

In this chapter we focus on immunorecognition of RNA by two members of the family of Toll-like receptors (TLRs), TLR7, and TLR8. While any long single-stranded RNA is readily recognized by both TLR7 and TLR8, sequencedependent activation of TLR7 and TLR8 becomes more evident when using short RNA oligonucleotides. RNA oligonucleotides containing sequence motifs for TLR7 and TLR8 are termed is RNA (immunostimulatory RNA). Moreover, short doublestranded RNA oligonucleotides as used for siRNA (short interfering RNA) containing such sequences function primarily as ligands for TLR7 but not TLR8. Even in the presence of appropriate sequence motifs, RNA is not detected by TLR7 and TLR8 when certain chemical modifications are present. Both immunological recognition and ignorance are relevant for the development of RNA-based therapeutics, depending on the clinical setting for which they are developed.