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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-12

AUTHORS

Noemi Poerio, Francesca Bugli, Francesco Taus, Marilina B Santucci, Carlo Rodolfo, Francesco Cecconi, Riccardo Torelli, Francesco Varone, Riccardo Inchingolo, Fabio Majo, Vincenzina Lucidi, Sabrina Mariotti, Roberto Nisini, Maurizio Sanguinetti, Maurizio Fraziano

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. More... »

PAGES

45120

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/srep45120

DOI

http://dx.doi.org/10.1038/srep45120

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1084132968

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28345623


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