Tri-mannose grafting of chitosan nanocarriers remodels the macrophage response to bacterial infection

• Published in: Journal of nanobiotechnology 2019-01, Vol.17 (1), p.15-15, Article 15
• Main Authors: Coya, Juan Manuel, De Matteis, Laura, Giraud-Gatineau, Alexandre, Biton, Anne, Serrano-Sevilla, Inés, Danckaert, Anne, Dillies, Marie-Agnès, Gicquel, Brigitte, De la Fuente, Jesus M, Tailleux, Ludovic
• Format: Article
• Language: English
• Subjects: Actin; Antibiotics; Antimicrobial agents; Bacteria; Bacterial infections; Bacteriology; BCG; Bedaquiline; Biodegradation; Bioengineering; Biomaterials; Cancer therapies; Chitin; Chitosan; Chitosan nanocarriers; Cytoskeleton; Death; Drug delivery; Drug delivery systems; Drug resistance; Drug therapy; Drugs; Embryos; Gene sequencing; Genes; Glucose metabolism; Grafting; Health; Health aspects; Health risks; Host response; Human behavior; Immune system; Immunosuppressive agents; Infection; Infections; Infectious diseases; Life Sciences; Ligands; Lysosomes; Macrophages; Mannose; Messenger RNA; Metabolism; Microbiology and Parasitology; Monosaccharides; mRNA; Muscle proteins; Mycobacterium tuberculosis; Nanoparticles; Nanotechnology; Oxidative metabolism; Oxidative phosphorylation; Phosphorylation; Physiological aspects; Properties; RNA; RNA sequencing; Side effects; Sugar; Surface grafting; Tuberculosis
• ISSN: 1477-3155; 1477-3155
• DOI: 10.1186/s12951-018-0439-x

Infectious diseases are still a leading cause of death and, with the emergence of drug resistance, pose a great threat to human health. New drugs and strategies are thus urgently needed to improve treatment efficacy and limit drug-associated side effects. Nanotechnology-based drug delivery systems are promising approaches, offering hope in the fight against drug resistant bacteria. However, how nanocarriers influence the response of innate immune cells to bacterial infection is mostly unknown. Here, we used Mycobacterium tuberculosis as a model of bacterial infection to examine the impact of mannose functionalization of chitosan nanocarriers (CS-NCs) on the human macrophage response. Both ungrafted and grafted CS-NCs were similarly internalized by macrophages, via an actin cytoskeleton-dependent process. Although tri-mannose ligands did not modify the capacity of CS-NCs to escape lysosomal degradation, they profoundly remodeled the response of M. tuberculosis-infected macrophages. mRNA sequencing showed nearly 900 genes to be differentially expressed due to tri-mannose grafting. Unexpectedly, the set of modulated genes was enriched for pathways involved in cell metabolism, particularly oxidative phosphorylation and sugar metabolism. The ability to modulate cell metabolism by grafting ligands at the surface of nanoparticles may thus be a promising strategy to reprogram immune cells and improve the efficacy of encapsulated drugs.