Toll Meets Bacterial CpG-DNA Hermann Wagner  Immunity  Volume 14, Issue 5, Pages 499-502 (May 2001) DOI: 10.1016/S1074-7613(01)00144-3

Figure 1 Signaling Pathway Activated by TLR9 Bacterial CpG-DNA or mimicking CpG-ODN first binds to a cell surface DNA binding protein. Binding is sequence independent and does not bring about cell activation but rather endocytosis. Upon endosomal maturation/acidification, immunostimulatory CpG motifs become sequence-specifically engaged by TLR9. Activated TLR9 recruits the adaptor protein MyD88 followed by IRAK and TRAF6. Ligands for IL-1R, IL-18R, TLR2, and TLR4 essentially trigger a similar signal cascade, while CD40L expressing T helper cells interact at the level of TRAF6. Arguments supporting the involvement of MyD88, TRAF6, Iκ kinase α/β, and TLR9 are exclusively based on experiments using dominant-negative forms of the respective proteins, genetic complementation with TLRs of nonresponder cells, and analysis of MyD88- or TLR9-deficient mice. The glycosyl-phosphatilinositol linked CD14 molecule lacks a signal transduction moiety of its own and is thought to scavenge LPS opsonized by LPS binding protein (LBP) for recognition by TLR4, and assisted by MD2. All molecules in the figure are symbols only—their shapes are not based on biochemical data. Solid arrows indicate direct interactions. Broken arrows are used where direct interactions has not been demonstrated Immunity 2001 14, 499-502DOI: (10.1016/S1074-7613(01)00144-3)