Different molecular responses of Mytilus mantle to lipopolysaccharide and peptidoglycan challenges

Mytilus live in water as sessile filter feeders, and the mantle tissue plays an important role in their immune defense. However, the overall knowledge of the immunity of this tissue remains limited. Peptidoglycan (PGN) and lipopolysaccharide (LPS) are the most representative microbe-associated molecular patterns (MAMPs) that play roles in the immune stimulation of host cells. In the present study, ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS)-based metabolomic analysis was performed to understand the precise regulatory mechanism at the molecular level in the Mytilus mantle in response to PGN and LPS stress. Moreover, the antioxidant ability and free amino acid composition of the mantle, and the antimicrobial activities of mantle mucus were evaluated. Our results revealed that LPS and PGN stresses had different effects on the mantle's free amino acid composition and antioxidant ability, and the mantle mucus' antimicrobial activity. Both PGN and LPS stress-induced alterations in amino acids, phospholipids, fatty acids, nucleotides, and their derivatives in the mantle. PGN injection activated the amino acid-related metabolism, and inhibited the lipid-related metabolisms in the mantle, while LPS injection activated the amino acid-related metabolisms and inhibited the arachidonic acid metabolism in the mantle compared to that in the control group. In addition, activation of the mTOR and FoxO signaling pathways and inhibition of lipid-related metabolism were observed in PGN vs. LPS. In addition, PGN injection induced the upregulation of fosfomycin and deoxynojirimycin in the mantle compared to LPS injection. Our study highlights the different responses at the metabolomic level of the mussel mantle to different MAMPs and the potential application of metabolites that specifically respond to PGN and LPS challenges in mussels as biomarkers.