Figure 2.

The LPS transfer cascade. The transfer of LPS to TLR4–MD2 through LBP and CD14 massively amplifies the host response to extracellular LPS. (1) LBP binds longitudinally to a LPS micelle. (2) Electrostatic interactions form between LBP (bound to LPS) and CD14. (3) LPS is transferred to CD14 in multiple rounds of transfer. (4) LPS is transferred from CD14 to MD2 by interacting with the LRR13–LRR15 domain of TLR4. (5) The receptor complex of TLR4–MD2 and LPS dimerises. (6) This results in signal activation by TLR4–MD2. (7) Signalling proceeds through MYD88-dependent and MYD88-independent pathways. (8) TLR4 cooperates with various co-receptors. LPS aggregates that have been intercalated into the plasma membrane by LBP may induce mechanical stress on transmembrane proteins and ion channels and contribute to LPS signalling. Adapted from. ¹⁶⁵