Macrophage membrane-coated nanoparticles control pathological inflammation and enhance survival in models of severe bacterial pneumonia

RATIONALE: Severe bacterial pneumonia is a leading cause of death worldwide, and mortality rates remain unacceptably high despite appropriate antibiotic treatment. Macrophage membrane-coated nanoparticles (MΦ-NPs) are biomimetic constructs engineered to neutralize bacterial toxins, pathogen-associated molecular patterns, and proinflammatory cytokines. OBJECTIVE: To evaluate the therapeutic potential of MΦ-NPs for the treatment of severe bacterial pneumonia. METHODS: We evaluated the therapeutic potential of MΦ-NPs using in vitro models of infection involving human lung endothelial and epithelial cells, as well as primary human neutrophils, and in vivo murine models of Pseudomonas aeruginosa (PA) and methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. MAIN RESULTS: MΦ-NPs demonstrated potent cytoprotective and anti-inflammatory activity in vitro, without impairing neutrophil antimicrobial function. In both PA and MRSA pneumonia models, MΦ-NP treatment significantly improved survival, reduced bacterial burden, lowered proinflammatory cytokines, and preserved lung architecture. Quantitative proteomics further revealed suppression of inflammatory, coagulation, and fibrotic pathways associated with poor outcomes in human pneumonia and ARDS. CONCLUSIONS: These findings establish MΦ-NPs as a promising host-directed therapeutic strategy for mitigating the deleterious inflammatory sequelae of severe bacterial pneumonia.