Direct interaction between <i>Lactiplantibacillus plantarum</i> ZJ316-derived lipoteichoic acid and TLR2 mediates anti-inflammatory and barrier-protective effects in intestinal cells

Lipoteichoic acid (LTA), a key bioactive substance of the Gram-positive bacterial cell wall, has garnered attention for its immunomodulatory properties. Herein, we investigated the underlying molecular mechanism by which LTA derived from <i>Lactiplantibacillus plantarum</i> ZJ316 exerts anti-inflammatory effects through interaction with Toll-like receptor 2 (TLR2). Molecular docking, dynamics simulations, and surface plasmon resonance (SPR) indicated a strong and specific binding affinity (<i>K</i>_D = 1.02 μM), with key residues (<i>e.g.</i>, Lys422, Arg486, Arg508) involved in stabilizing the LTA-TLR2 complex. Using an <i>in vitro</i> inflammatory model of Caco-2 cells induced by macrophage supernatant, we demonstrated that LTA significantly upregulated TLR2 expression and inhibited the ERK and p38 MAPK phosphorylation, resulting in reduced secretion of pro-inflammatory cytokines (TNF-α, IL-8) and enhanced anti-inflammatory IL-10 expression. Furthermore, LTA protected intestinal epithelial barrier function by enhancing the expression of tight junction proteins (ZO-1, Occludin, and Claudin-1). These findings highlight the potential of <i>L. plantarum</i> ZJ316-derived LTA as a bioactive component for intestinal health and provide new insight into its regulatory mechanism <i>via</i> the TLR2-MAPK signaling pathway.