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The "trinity" of nucleic acid recognizing Toll-like receptors (TLRs) is the focus of intense research efforts. Among the plethora of pattern recognition receptors the ones that recognize RNA and DNA always seemed Janus-faced in their potential - dangerous, but also promising. Therefore manipulating TLR3, TLR7 and TLR9, which recognize dsRNA-, ssRNA- and CpG-containing DNA, respectively, is a very attractive goal, because increasing evidence shows that both suppression or enhancement of the immune system might thereby be achieved. In this review we try to illustrate the current knowledge of the endosomal nucleic acid recognizing TLRs. We then want to extend our view beyond the pathogen recognizing capacity to their role in autoimmunity and cancer. Significant progress has been made in our understanding of the structure of TLRs, signaling pathways and ligand identity. The question of if and how we can translate this into new specific immunosuppressive drugs or anti-cancer adjuvants is discussed.

Nucleic acid recognizing Toll-like receptors as therapeutic targets: a focus on autoimmunity and cancer