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Harnessing phages in the age of antibiotic resistance: immunological perspectives

Tasnime A Abdo Ahmad1, Dina Kabbara1, Zahraa Shokor1

  • 1Department of Experimental Pathology, Immunology and Microbiology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.

Frontiers in Immunology
|August 14, 2026
PubMed

Insights

Antimicrobial resistance (AMR) drives phage therapy interest. Phages interact with the immune system, affecting treatment efficacy. Immune-aware strategies are crucial for successful phage therapy against resistant infections.

Area of Science:

  • Microbiology
  • Immunology
  • Pharmacology

Background:

  • The rise of antimicrobial resistance (AMR) necessitates novel therapeutic strategies.
  • Bacteriophages (phages) are explored as precision antibacterial agents due to their specificity.
  • Phages can interact with host immune pathways, impacting their therapeutic potential.

Purpose of the Study:

  • To review the complex interactions between bacteriophages and the host immune system.
  • To distinguish direct immune recognition of phage components from indirect immune activation.
  • To discuss immune-aware strategies for optimizing phage therapy development.

Main Methods:

  • Integration of mechanistic, translational, and clinical evidence.
  • Analysis of innate immune mechanisms (complement, phagocytes, PRRs, neutrophils).
  • Evaluation of adaptive immune responses (antibodies, neutralization).

Main Results:

  • Phage components, nucleic acids, and impurities can trigger innate and adaptive immunity.
  • Immune responses influence phage pharmacokinetics, persistence, and inflammatory reactions.
  • Anti-phage antibodies do not consistently predict treatment failure in clinical settings.

Conclusions:

  • Phage-immune interactions are critical determinants of therapeutic outcomes.
  • Understanding these interactions is key to developing effective phage therapies.
  • Immune-aware strategies are essential for advancing phage therapy for multidrug-resistant infections.
Keywords:
antimicrobial resistanceimmunogenicityimmunomodulationinnate and adaptive immunitiesneutralizing antibodiesphage engineeringphage therapyphages

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