A bacterially engineered macrophage sponge as a neutralization decoy to treat bacterial infection

Antibiotic-resistant strains have emerged, and endotoxins vary greatly in their structural motifs across bacterial species, limiting the clearance efficiency of structure-specific anti-endotoxin antibodies. This study constructs intracellularly gelated macrophages (GMs) with an intact membrane structure to neutralize bacteria and endotoxins via receptor-ligand interaction and share the bacterial burden to ameliorate in vivo infection without considering their molecular structure. Furthermore, GMs derived from bacterially infected macrophages (here referred to as bacterially engineered macrophages) are found to have upregulated membrane pathogen-related receptors for strengthened bacterium and endotoxin recognition and increased the membrane zeta potential to reduce the electrostatic repulsion force for facile GM-bacterium surface interaction. Bacterially engineered GMs achieve efficient management of sepsis and wound infection and targeted alleviation of bacterial pneumonia. The top-down fabrication of GMs provides a universal neutralization strategy against bacterial infection, and bacterially engineered host immune cells, upon intracellular gelation, demonstrate a natural cell engineering venue to obtain comprehensive neutralization decoys.