Biodegradable microparticles promote anti-inflammatory innate immune memory through a size- and mTOR-dependent...

Area of Science:

• Immunology
• Biomaterials Science
• Nanotechnology

Background:

• Innate immune cells exhibit memory beyond microbial stimuli.
• Biomaterials can modulate innate immune responses for therapeutic benefit.
• Particle characteristics influence immune cell interactions.

Purpose of the Study:

• Investigate particle size as a determinant of innate immune memory.
• Characterize the effects of poly(lactic-co-glycolic acid) particles on macrophage activation and memory.
• Explore the therapeutic potential of size-tuned biomaterials for immune modulation.

Main Methods:

• Utilized biodegradable poly(lactic-co-glycolic acid) particles of varying sizes.
• Assessed macrophage activation and phenotype using in vitro assays.
• Analyzed cytokine secretion (IL-10, IL-1Ra) and metabolic pathways (oxidative phosphorylation, mTOR signaling).
• Evaluated in vivo innate immune memory in mouse models.

Main Results:

• 1-2 µm poly(lactic-co-glycolic acid) particles induced an anti-inflammatory macrophage phenotype.
• These particles enhanced oxidative phosphorylation via mTOR signaling.
• Exposure led to durable anti-inflammatory reprogramming with elevated IL-10 and IL-1 receptor antagonist secretion.
• In vivo studies showed persistent reprogramming of bone marrow cells up to one week post-injection.

Conclusions:

• Particle size is a critical factor in modulating innate immune responses and memory.
• Specific size ranges of biodegradable polymers can induce beneficial anti-inflammatory immune training.
• Findings highlight the potential of tailored biomaterials for therapeutic immune reprogramming.