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Scientists Discover Lipid-Based Gut-Immune Communication Pathway

New research identifies how APOL9 proteins selectively bind bacterial lipids to enhance immune responses, offering potential for microbiota-targeted therapies.

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Overview

  • The study reveals that the protein APOL9, induced by gut microbiota, binds to ceramide-1-phosphate (Cer1P) on Bacteroidales bacteria to trigger immune-modulating effects.
  • APOL9 binding prompts bacteria to release outer membrane vesicles (OMVs), which enhance interferon-gamma signaling and increase MHC-II expression on intestinal cells.
  • Mice lacking APOL9 exhibit weakened immunity and greater susceptibility to Salmonella infection, but OMV treatment restores immune function and reduces infection severity.
  • Researchers developed the innovative 'APOL9-seq' method to map bacterial targets of APOL9, demonstrating specificity for Bacteroidales species.
  • The study highlights potential therapeutic applications, including leveraging human APOL2, which shows conserved binding to bacterial lipids, to strengthen gut immunity.