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Updated: Sep 18, 2025

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BCG-Derived Outer Membrane Vesicles Induce TLR2-Dependent Trained Immunity to Protect Against Polymicrobial Sepsis.

Yuan Gong1,2, Wenyan Hao1, Lingqi Xu1

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Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|June 24, 2025
PubMed
Summary

BCG-derived outer membrane vesicles (B-OMVs) offer a safe and effective way to induce trained immunity, enhancing host defense against sepsis. These vesicles show promise as a novel immunomodulatory agent for sepsis treatment.

Keywords:
BCGOMVssepsistrained immunity

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Area of Science:

  • Immunology
  • Infectious Diseases
  • Vaccinology

Background:

  • Sepsis is a critical care mortality cause, necessitating novel host defense strategies.
  • Trained immunity offers innate immune memory to bolster host defense.
  • Bacillus Calmette-Guérin (BCG) induces trained immunity but has adverse reactions.

Purpose of the Study:

  • To investigate BCG-derived outer membrane vesicles (B-OMVs) as a safe and effective inducer of trained immunity against sepsis.
  • To evaluate the safety and efficacy of B-OMVs compared to conventional vaccines.
  • To elucidate the underlying mechanisms of B-OMV-mediated trained immunity.

Main Methods:

  • Characterization and safety assessments of B-OMVs.
  • Experimental polymicrobial sepsis models.
  • Analysis of hematopoietic stem cell expansion and myelopoiesis.
  • Toll-like receptor 2 (TLR2) pathway activation studies, including aerobic glycolysis and epigenetic reprogramming.
  • Assessment of bone marrow-derived macrophage phagocytic activity.

Main Results:

  • B-OMVs effectively triggered trained immunity and protected against experimental sepsis.
  • B-OMVs demonstrated no significant toxicity or pathological effects.
  • Mechanisms involved TLR2-dependent activation of aerobic glycolysis and epigenetic reprogramming, promoting myelopoiesis.
  • Enhanced immune response and phagocytic activity in macrophages were observed.

Conclusions:

  • B-OMVs represent a novel, safe, and effective immunomodulatory agent for combating sepsis-induced immune dysfunction.
  • B-OMVs show translational potential as an alternative to BCG vaccines for inducing trained immunity.
  • This study highlights B-OMVs as a promising strategy to enhance host defense against sepsis.