Immune-modulatory effects and mechanism of action of L-theanine on ETEC-induced immune-stressed mice via nucleotide-binding oligomerization domain-like receptor signaling pathway

L-Theanine (LTA), a non-protein-derived amino acid, is widely used as a functional ingredient. Here, we established an immune-stressed mouse model by infecting mice with enterotoxigenic Escherichia coli (ETEC) to study the immunomodulatory effects of LTA with respect to nucleotide-binding oligomerization domain (NOD)-like receptor signaling in vivo. Compared to ETEC control group, LTA alleviated ileal tissue lesions, significantly attenuated interleukin-1 beta (IL-1 beta) and tumor necrosis alpha (TNF alpha) overexpression, which was consistent with their protein levels. Additionally, LTA inhibited the ETEC-induced overexpression of NOD2 and receptorinteracting protein 2 (RIP2) proteins and mRNAs, TGE-beta-activated kinase 1 (TAK1) and proteasome subunit alpha type-7 (PSMA7) mRNAs, and partially decreased nuclear factor-kappa B (NF-kappa B) p65 protein levels. Furthermore, it suppressed c-Jun NH2-terminal kinase 1/2 (JNK1/2), extracellular signal-regulated kinase 1/2 (ERK1/2), and p38 mitogen-activated protein kinase (p38) phosphorylation. Thus, we demonstrated that LTA regulates the innate immunity of ETEC-induced immune-stressed mice via NOD1/2-NF-kappa B and NOD1/2-MAPK pathways.