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Sci Rep. 2017 Mar 27;7:45120. doi: 10.1038/srep45120.

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

Author information

1
Department of Biology, University of Rome Tor Vergata Rome, Italy.
2
Institute of Microbiology, Fondazione Policlinico Universitario Gemelli - Catholic University of Sacred Heart, Rome, Italy.
3
Unit of Cell Stress and Survival, Danish Cancer Society Research Center, Copenhagen, Denmark.
4
Department of Pediatric Hematology and Oncology, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.
5
Department of Pulmonary Medicine, Fondazione Policlinico Universitario Gemelli - Catholic University of Sacred Heart, Rome, Italy.
6
Cystic Fibrosis Unit, Paediatric Hospital "Bambino Gesù", Rome, Italy.
7
Department of Infectious, Parasitic and Immunomediated Diseases, Istituto Superiore di Sanità, Rome, Italy.

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.

PMID:
28345623
PMCID:
PMC5366871
DOI:
10.1038/srep45120
[Indexed for MEDLINE]
Free PMC Article

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