Immunostimulatory activity of lipoteichoic acid with three fatty acid residues derived from <i>Limosilactobacillus antri</i> JCM 15950 ^T

Some lactic acid bacteria activate the host intestinal immune system via toll-like receptor (TLR) 2. Lipoteichoic acid (LTA) is a TLR2 ligand; however, the moieties of LTA that determine its immunostimulatory activity remain unclear because of the wide diversity of LTA partial structures. We found that <i>Limosilactobacillus antri</i> JCM 15950^T has three types of LTAs (triacyl, diacyl, and monoacyl LTAs). Specifically, structural analysis of the LTAs revealed that triacyl LTA plays a crucial role in immunostimulation and that the fatty acid residues are essential for the activity. The three acyl residues are characteristic of LTAs from many lactic acid bacteria, and our findings can explain the immunostimulatory mechanisms widely exhibited by lactic acid bacteria. Furthermore, the immunostimulatory activity of membrane vesicles released by <i>L. antri</i> JCM 15950^T is due to the transferred LTA, demonstrating a novel mechanism of membrane vesicle-mediated immunostimulation.