Morphology-Engineered Bioparticles Drive Trained Immunity via TLR1/MAPK/mTOR–Redox–Methylation Hub for Broad-Spectrum Protection against MDR Pathogens

Further studies provide evidence supporting the hypothesis that fBLP triggers a trained immune-like phenotype in vitro and in vivo, independent of antigen specificity. This includes an increase in macrophage phagocytosis, moderate secretion of pro-inflammatory cytokines, and alterations in metabolic pathways. fBLP-triggered trained immunity alters receptor activation via the TLR1/MAPK/mTOR signaling pathway, promoting metabolic reprogramming, as evidenced by enhanced glycolysis, increased accumulation of TCA cycle metabolites, and alterations in amino acid and lipid metabolism.

These processes involve epigenetic modifications, such as deacetylation and demethylation, which selectively amplify MAPK pathway activation and induce unique metabolic changes. Collectively, these alterations establish an immune memory state. This study pioneers the integration of morphology engineering and trained immunity, offering an innovative strategy to disease prevention and the design of anti-infective vaccines.