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

Poerio, N., Bugli, F., Taus, F., Santucci, M. B., Rodolfo, C., Cecconi, F., Torelli, R., Varone, F., Inchingolo, R., Majo, F., Lucidi, V., Mariotti, S., Nisini, R., Sanguinetti, M., Fraziano, M., Liposomes loaded with bioactive lipids enhance antibacterial innate immunity irrespective of drug resistance, <<SCIENTIFIC REPORTS>>, 2017; 7 (2017): 45120-N/A. [doi:10.1038/srep45120] [http://hdl.handle.net/10807/98184]

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

Bugli, Francesca
Secondo
;
Torelli, Riccardo;Varone, Francesco;Inchingolo, Riccardo;Sanguinetti, Maurizio
Penultimo
;
2017

Abstract

Phagocytosis is a key mechanism of innate immunity, and promotion of phagosome maturation may represent a therapeutic target to enhance antibacterial host response. Phagosome maturation is favored by the timely and coordinated intervention of lipids and may be altered in infections. Here we used apoptotic body-like liposomes (ABL) to selectively deliver bioactive lipids to innate cells, and then tested their function in models of pathogen-inhibited and host-impaired phagosome maturation. Stimulation of macrophages with ABLs carrying phosphatidic acid (PA), phosphatidylinositol 3-phosphate (PI3P) or PI5P increased intracellular killing of BCG, by inducing phagosome acidification and ROS generation. Moreover, ABLs carrying PA or PI5P enhanced ROS-mediated intracellular killing of Pseudomonas aeruginosa, in macrophages expressing a pharmacologically-inhibited or a naturally-mutated cystic fibrosis transmembrane conductance regulator. Finally, we show that bronchoalveolar lavage cells from patients with drug-resistant pulmonary infections increased significantly their capacity to kill in vivo acquired bacterial pathogens when ex vivo stimulated with PA-or PI5P-loaded ABLs. Altogether, these results provide the proof of concept of the efficacy of bioactive lipids delivered by ABL to enhance phagosome maturation dependent antimicrobial response, as an additional host-directed strategy aimed at the control of chronic, recurrent or drug-resistant infections.
Inglese
Poerio, N., Bugli, F., Taus, F., Santucci, M. B., Rodolfo, C., Cecconi, F., Torelli, R., Varone, F., Inchingolo, R., Majo, F., Lucidi, V., Mariotti, S., Nisini, R., Sanguinetti, M., Fraziano, M., Liposomes loaded with bioactive lipids enhance antibacterial innate immunity irrespective of drug resistance, <<SCIENTIFIC REPORTS>>, 2017; 7 (2017): 45120-N/A. [doi:10.1038/srep45120] [http://hdl.handle.net/10807/98184]
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