Lactobacillus plantarum lipoteichoic acid down-regulated Shigella flexneri peptidoglycan-induced inflammation

Bacterial peptidoglycans (PGNs) are recognized by the host’s innate immune system. This process is mediated by the NOD/CARD family of proteins, which induces inflammation by activating nuclear factor (NF)-κB. Excessive activation of monocytes by Shigella flexneri PGN (flexPGN) leads to serious inflammatory diseases such as intestinal bowel diseases (IBD) and Crohn’s disease. In this study, we examined whether Lactobacillus plantarum lipoteichoic acid (pLTA) could attenuate the pro-inflammatory signaling induced by flexPGN in human monocytic THP-1 cells. Compared to control THP-1 cells, pLTA-tolerant cells showed a significant reduction in TNF-α and IL-1β production in response to flexPGN. We also examined the inhibition of NF-κB and the activation of mitogen-activated protein kinase (MAPK) in pLTA-tolerant cells. We found that the expression of NOD2 in pLTA-tolerant cells was down-regulated at the mRNA and protein levels, suggesting that pLTA is a potent modulator of the pro-inflammatory NOD2-related signaling pathways induced by flexPGN. Together, these data indicate that pLTA induces cross-tolerance against flexPGN. Notably, these effects are related not only to IL-1 signaling, which is known to play a role in LPS tolerance, but also to NOD-Rick signaling. This study provides insight into how commensal microflora may contribute to homeostasis of the host intestinal tract.