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6d ago

Study Reveals Host Protein APOL9's Role in Gut Microbiota-Driven Immune Modulation

Published in *Nature*, the research uncovers how APOL9 selectively targets bacterial lipids to release immune-boosting vesicles, offering insights into microbiome-directed therapies.

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Overview

  • APOL9, a host protein, selectively binds to ceramide-1-phosphate (Cer1P), a lipid found on Bacteroidales bacteria, enabling precise microbial targeting.
  • Unlike traditional antimicrobial proteins, APOL9 induces the release of outer membrane vesicles (OMVs) from Bacteroidales rather than killing them.
  • OMVs enhance mucosal immunity by boosting interferon-gamma (IFN-γ) signaling and increasing MHC-II expression, essential for training specialized gut T cells.
  • Mice lacking APOL9 showed weaker immune responses to Salmonella infections, but administering OMVs restored immune function and reduced infection severity.
  • Researchers are now investigating APOL9’s human homolog, APOL2, and exploring therapeutic strategies to modulate this lipid-based communication pathway.