Effect of infected bone marrow suspension on gene expression in RAW264.7 macrophages

Bacterial infectious diseases have posed a serious challenge to public health, often resulting in treatment failure and infection recurrence due to the emergence of drug-resistant bacteria. Owing to inaccessible binding sites, pathogens can evade attack from host immune cells and traditional antibiotics, leading to local immunosuppressive status. Our study reports a novel bacteriophage-based immune scavenger labeling nanoplatform (Mn2+@Man-phage) to combat immune-evasive bacteria and reverse immunosuppressive status. Our nanosystem utilizes the inherent bacterium-targeting ability of bacteriophages to aggregate at infection sites and mediates mannose-dependent recognition, phagocytosis, and killing of bacteria by macrophages, while the released Mn2+ amplifies the antibacterial immune efficacy. Consequently, macrophages polarize towards M1 and secrete various pro-inflammatory factors, effectively clearing bacteria. Moreover, reprogramming macrophages directly activate T cells at infection sites, eliciting potent adaptive antibacterial immune responses and ultimately achieving bacterial eradication. Overall, we demonstrate a universal strategy for pathogen targeting and immunomodulation of macrophages against bacterial infection.