Liposomes loaded with bioactive lipids enhance antibacterial innate immunity irrespective of drug resistance

摘要: Phagocytosis is a key mechanism of innate immunity, and promotion phagosome maturation may represent therapeutic target to enhance antibacterial host response. Phagosome favored by the timely coordinated intervention lipids be altered in infections. Here we used apoptotic body-like liposomes (ABL) selectively deliver bioactive cells, then tested their function models pathogen-inhibited host-impaired maturation. Stimulation macrophages with ABLs carrying phosphatidic acid (PA), phosphatidylinositol 3-phosphate (PI3P) or PI5P increased intracellular killing BCG, inducing acidification ROS generation. Moreover, PA enhanced ROS-mediated Pseudomonas aeruginosa, expressing pharmacologically-inhibited naturally-mutated cystic fibrosis transmembrane conductance regulator. Finally, show that bronchoalveolar lavage cells from patients drug-resistant pulmonary infections significantly capacity kill vivo acquired bacterial pathogens when ex stimulated PA- PI5P-loaded ABLs. Altogether, these results provide proof concept efficacy delivered ABL dependent antimicrobial response, as an additional host-directed strategy aimed at control chronic, recurrent