Programmable macrophage interface engineering enables targeted antibacterial therapy in immunosuppressed infections

Area of Science:

• Immunology
• Microbiology
• Biotechnology

Background:

• Severe bacterial infections are challenging due to antimicrobial resistance and immune dysfunction.
• A conserved hypofunctional macrophage state impairs pathogen clearance in infections.

Purpose of the Study:

• To develop a non-genetic immune cell engineering strategy to enhance macrophage antibacterial activity.
• To overcome infection-induced immune dysfunction for improved therapeutic outcomes.

Main Methods:

• Engineered macrophages using membrane-fusogenic liposomes functionalized with bacteriophage proteins.
• Loaded liposomes with intracellular antibiotics for targeted delivery.
• Analyzed clinical transcriptomic data and tested efficacy in mouse infection models.

Main Results:

• Engineered macrophages showed enhanced bacterial capture, immobilization, and intracellular killing.
• Treatment in mouse models achieved near-complete pathogen clearance and reduced inflammation.
• Reversed immune dysfunction and restored coordinated immune responses.

Conclusions:

• Macrophage interface engineering is a viable strategy to combat severe bacterial infections.
• This approach overcomes immune dysfunction and enables targeted antibacterial therapy.
• Provides a potential platform for treating challenging infections.