Beyond its established functions in inflammation and immune signaling, HMGB1 acts as an important component of mucosal host defense, helping maintain the balance between the gut microbiota and intestinal tissues.
A recent study identifies a previously unrecognized HMGB1–ToH1 molecular feedback loop that directly regulates these interactions. In response to the intestinal microbiota, HMGB1 is released into the colonic mucus, where it recognizes and binds a conserved amino acid sequence termed Target of HMGB1 (ToH1), present in proteins exposed on the bacterial surface.
This interaction triggers several protective mechanisms:
- Bacterial aggregation: HMGB1 binding promotes bacterial clustering, limiting bacterial access to the intestinal epithelial surface.
- Inhibition of bacterial adhesion: by interacting with ToH1-containing surface proteins, HMGB1 interferes with bacterial attachment to host tissues and restricts mucosal invasion.
- Microbial adaptation: commensal bacteria exposed to HMGB1 downregulate the expression of ToH1-bearing adhesins, establishing a feedback mechanism that modifies bacterial adhesive behavior.
These findings expand the biological significance of HMGB1 beyond its well-established role as a damage-associated molecular pattern (DAMP).
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Read the full article about the study
