Tri-mannose grafting of chitosan nanocarriers remodels the macrophage response to bacterial infection.
Bacterial Infections
/ immunology
Cells, Cultured
Chitosan
/ chemistry
Drug Carriers
/ chemistry
Drug Delivery Systems
Host-Pathogen Interactions
/ drug effects
Humans
Immunity, Innate
/ drug effects
Macrophages
/ drug effects
Mannose
/ chemistry
Metabolic Networks and Pathways
/ drug effects
Mycobacterium tuberculosis
/ physiology
Nanoparticles
/ chemistry
Phagocytosis
Transcriptome
/ drug effects
Chitosan nanocarriers
Host response
Macrophages
Mycobacterium tuberculosis
Surface grafting
Journal
Journal of nanobiotechnology
ISSN: 1477-3155
Titre abrégé: J Nanobiotechnology
Pays: England
ID NLM: 101152208
Informations de publication
Date de publication:
25 Jan 2019
25 Jan 2019
Historique:
received:
11
10
2018
accepted:
31
12
2018
entrez:
27
1
2019
pubmed:
27
1
2019
medline:
15
6
2019
Statut:
epublish
Résumé
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.
Sections du résumé
BACKGROUND
BACKGROUND
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.
RESULTS
RESULTS
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.
CONCLUSIONS
CONCLUSIONS
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.
Identifiants
pubmed: 30683129
doi: 10.1186/s12951-018-0439-x
pii: 10.1186/s12951-018-0439-x
pmc: PMC6346558
doi:
Substances chimiques
Drug Carriers
0
Chitosan
9012-76-4
Mannose
PHA4727WTP
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
15Subventions
Organisme : FP7 Health
ID : 604237
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