Role of TLR/NF-κB/MAPK signaling pathways in mastitis pathogenesis and their potential as therapeutic targets – a review

Mastitis, a prevalent infectious disease characterized by mammary gland inflammation, represents a major economic burden and health challenge in dairy farming, necessitating comprehensive understanding of underlying molecular mechanisms for effective therapeutic intervention. This review investigates the crucial role of toll-like receptors (TLRs) in mastitis pathogenesis through recognition of key pathogens including Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). TLR activation triggers complex downstream signaling involving nuclear factor kappa B (NF-κB) and mitogen-activated protein kinases (MAPK) pathways, orchestrating inflammatory responses and disease progression in bovine mammary tissue. The interplay between these signaling networks controls pathogen recognition, inflammatory initiation, and disease resolution processes. Current research emphasizes oxidative stress-mediated inflammatory responses in mastitis development, elucidating disease mechanisms and therapeutic targets. Emerging strategies focus on modulating these pathways through natural compounds and pharmacological interventions, offering promising precision immunomodulatory approaches. Understanding the complexity of TLR/NF-κB/MAPK signaling is essential for developing targeted therapies that effectively combat this infectious disease while minimizing adverse effects. This comprehensive analysis of signaling mechanisms establishes a foundation for advancing veterinary medicine and improving dairy cattle health management through evidence-based therapeutic interventions, ultimately addressing the substantial economic impact of mastitis in the dairy industry.