Introduction

• Toll-Like Receptor 4 (TLR4) is a pattern recognition receptor in the body's defence system.
• Detects lipopolysaccharide (LPS) from gram-negative bacteria.
• Transformed understanding of immune system recognition and response.

Structural Organization and Ligand Recognition

• Structural Components:
• Leucine-rich repeat (LRR) extracellular domain
• Transmembrane region
• Intracellular Toll/IL-1 receptor (TIR) domain
• Co-receptor associations (MD-2, CD14)
• Activation requires a complex assembly process:
• LPS binding to CD14
• Transfer to MD-2/TLR4 complex
• Receptor dimerization
• Recruitment of adaptor proteins
• Signal cascade initiation
• Recognizes LPS, DAMPs, viral proteins, plant-derived compounds, synthetic compounds.

Signalling Pathways and Regulation

• Operates through two distinct pathways:
• MyD88-Dependent Pathway:
• Rapid inflammatory response
• NF-κB activation
• Pro-inflammatory cytokine production
• Early-phase response genes
• TRIF-Dependent Pathway:
• Type I interferon production
• Late-phase NF-κB activation
• Anti-viral response
• Endosomal signalling
• Regulatory Mechanisms:
• Membrane trafficking control
• Post-Translational modifications
• Negative feedback loops
• Cellular localization
• Expression level modulation

Physiological Functions and Disease Implications

• Role in multiple biological processes:
• Innate Immunity:
• Pathogen recognition
• Inflammatory response initiation
• Antimicrobial peptide production
• Phagocyte activation
• Adaptive Immunity Bridge:
• Dendritic cell maturation
• T-cell activation signals
• B-cell response modulation
• Immune memory development
• Disease Associations:
• Infectious Diseases: Sepsis, Bacterial infections, Viral responses, Fungal recognition
• Inflammatory Conditions: Atherosclerosis, Rheumatoid arthritis, Inflammatory bowel disease, Asthma
• Metabolic Disorders: Insulin resistance, Obesity, Fatty liver disease, Cardiovascular complications

Recent Advances and Therapeutic Applications

• Novel Functions: Tissue repair and regeneration, Metabolic regulation, Cancer immunity, Neuroinflammation
• Therapeutic Strategies:
• TLR4 Antagonists: Sepsis treatment, Anti-inflammatory agents, Autoimmune disease therapy, Pain management
• TLR4 Agonists: Vaccine adjuvants, Cancer immunotherapy, Immune system stimulation, Pathogen resistance enhancement
• Diagnostic Applications: Biomarker development, Disease monitoring, Treatment response prediction, Risk assessment

Future Perspectives

• Detailed studies uncovering mechanisms of ligand recognition and receptor activation.
• Single-cell level analysis for insights into cell responses and interactions.
• Ongoing therapeutic development targeting TLR4:
• Small Molecule Inhibitors: Prevention of excessive inflammation, Sepsis treatment, Chronic inflammatory disease management
• Monoclonal Antibodies: Selective pathway inhibition, Reduced side effects, Targeted therapeutic approach
• Novel Delivery Systems: Enhanced drug effectiveness, Reduced systemic effects, Improved therapeutic index
• Continuous research in inflammation, cancer immunity, and more for therapeutic prospects.

Suitable ELISA Kits

• TLR4 ELISA Kit
• Toll-Like Receptor 4 ELISA Kit