Toll-like receptor 4 (TLR4) (TLR4)

Toll-like receptor 4 (TLR4), also known as CD284, is a transmembrane pattern recognition receptor primarily expressed on innate immune cells like macrophages and dendritic cells, as well as microglia in the brain. It recognizes pathogen-associated molecular patterns (PAMPs) such as lipopolysaccharide (LPS) from Gram-negative bacteria and damage-associated molecular patterns (DAMPs) like HMGB1 released from damaged cells, forming complexes with MD-2 and CD14 to initiate signaling. TLR4 activates dual pathways: the MyD88-dependent pathway at the plasma membrane, leading to NF-κB and MAPK activation for pro-inflammatory cytokines (TNF-α, IL-6), and the TRIF-dependent endosomal pathway, promoting type I interferons (IFN-β) via IRF3. This orchestrates innate immunity, antigen presentation, and adaptive responses but contributes to pathology in noninfectious inflammation, sepsis, neurodegeneration, atherosclerosis, and aging-related "inflammaging." While no approved drugs directly target TLR4, antagonists aim to curb excessive inflammation in conditions like sepsis, posing challenges in balancing immune suppression against infection risk.

Other names

CD284

Drugs may act as antagonists to block LPS/DAMP binding and inhibit MyD88/TRIF pathways reducing pro-inflammatory cytokine production (e.g., TNF-α, IL-6); agonists activate pathways for vaccine enhancement