TLR4MD2Komplex

The TLR4MD2Komplex, also known as the TLR4/MD-2 complex, is the receptor assembly formed by Toll-like receptor 4 (TLR4) and the co-receptor MD-2 that detects bacterial lipopolysaccharide (LPS). It is expressed on the surface of many innate immune cells, such as macrophages and dendritic cells, and initiates signaling when extracellular LPS is present.

TLR4 is a type I transmembrane receptor with an extracellular leucine-rich repeat domain, a transmembrane segment, and a cytoplasmic TIR domain. MD-2, encoded by the LY96 gene, is a secreted glycoprotein that associates with the TLR4 ectodomain. The LPS-LBP-CD14 complex delivers LPS to the TLR4/MD-2 complex, promoting receptor dimerization and activation.

Activation of the TLR4MD2Komplex triggers two main signaling cascades. The MyD88-dependent pathway leads to NF-κB and AP-1 activation and rapid production of pro-inflammatory cytokines such as TNF, IL-6, and IL-1β. The TRIF-dependent pathway, engaged after endocytosis of the receptor, activates IRF3 and induces type I interferons.

The TLR4MD2Komplex is essential for host defense against Gram-negative bacteria; dysregulation contributes to sepsis and chronic inflammatory diseases. Genetic variations in LY96 or TLR4 can alter responsiveness. Therapeutic strategies aim to modulate this complex, including antagonists that block LPS binding or MD-2 function.