The dual immunomodulatory roles and signaling mechanisms of toll-like receptor 2 in different diseases

Toll-like receptors are important components of the pattern recognition receptor (PRR) family, and Toll-like receptor 2 (TLR2) is one of the most important Toll-like receptors involved in defending against infection and injury. TLR2 senses a wide array of pathogen- and damage-associated molecular patterns and has very broad functions in infectious diseases and other diseases. On one hand, TLR2 drives pro-inflammatory responses through the classical MyD88/NF-κB pathway, which is crucial for pathogen clearance; on the other hand, TLR2 can also limit excessive inflammation by activating the PI3K/Akt pathway, inducing IL-10, and promoting the expansion of regulatory T cells (Tregs), thereby maintaining immune tolerance. Such functional plasticity is regulated by ligand milieu, cell types and disease stages, and this underpins the dual roles of TLR2 under diverse pathological conditions including infection, inflammation, autoimmunity and organ transplantation. This review systematically summarizes advances in TLR2 signaling transduction and its immunological functions across various diseases and enables a more cautious evaluation of its pleiotropic effects in distinct disease contexts.