The immunobiology of the TLR9 subfamily

Members of the Toll-like receptor 9 (TLR9) subfamily are evolutionarily related and sense viral and bacterial infections at the endosomal subcellular compartment. Whereas TLR9 directly recognizes as ligands viral and bacterial CpG-DNA motifs, murine TLR7 and human TLR8 sense viral single stranded RNA motifs. Upon ligand-driven activation, members of the TLR9 subfamily bridge innate and adaptive immunity by activating immature antigen-presenting dendritic cells into professional antigen-presenting cells in a T helper cell-independent fashion. Cellular activation is strictly dependent on the adaptor molecule MyD88, as opposed to activation mediated by the TLR2–4 subfamilies, in which the adaptor molecules TIRAP, TRIF and TRAM come into play.