Rhamnose alleviates the proinflammatory response during endotoxemia via the CEACAM1/LGALS9-p38 axis.

Abstract

Gut microbiota plays an important role in orchestrating the host immune response. We previously reported that gut microbiota-derived rhamnose enhances the phagocytosis of macrophages, upon which we further asked whether rhamnose has modulatory effects on inflammation. Here, we show that, in an LPS-induced endotoxic mouse model, plasma rhamnose levels are increased. This bacteria-derived sugar alone does not impact inflammatory cytokine homeostasis or cause organ damage. In contrast, it is able to alleviate endotoxin-induced systemic inflammation and organ damage. Mechanistically, in macrophages in vitro, rhamnose binds to the V39, D40, and T101 sites of carcinoembryonic antigen-associated cell adhesion molecule 1 (CEACAM1), subsequently promoting the interaction between CEACAM1 and galectin 9 (LGALS9), which increases the protein level of dual-specificity protein phosphatase 1 (DUSP1). This inhibits p38 phosphorylation and thus attenuates the LPS-triggered expressions of proinflammatory factors. Collectively, our results suggest that rhamnose signals via the CEACAM1/LGALS9-p38 axis, which suppresses endotoxemia-associated inflammation, and that rhamnose is a candidate anti-inflammatory agent for the control of infection-induced organ damage.