Tri-mannose grafting of chitosan nanocarriers remodels the macrophage response to bacterial infection
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ABSTRACT:
PROVIDER: PRJNA495462 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7992050.fastq.gz | Fastqsanger.gz | |||
| SRR7992060.fastq.gz | Fastqsanger.gz | |||
| SRR7992051.fastq.gz | Fastqsanger.gz | |||
| SRR7992061.fastq.gz | Fastqsanger.gz | |||
| SRR7992052.fastq.gz | Fastqsanger.gz |
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Project description: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: 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: 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.
2018-10-11 | GSE121049 | GEO
Project description: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: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: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.
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Project description:Mannose remodels glucose metabolism to antagonize the overwhelming host inflammatory response
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Project description:we performed transcriptomic analysis in A549 cells and demonstrated a reduced proinflammatory response but increased host tolerance upon H1N1 virus infection and mannose therapy, providing further evidence for the beneficial role of mannose in immunometabolism.
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Project description:We treated Arabidopsis seedlings with chitosan and carried out a transcript profiling analysis (GeneChip microarrays) in order to identify genes and transcription factors regulated by chitosan. The results showed that jasmonate and defense responsive genes, camalexin and lignin biosynthetic genes were among genes up-regulated by chitosan. Several transcription factors are also strongly induced by chitosan. The results suggested that chitosan can be used as a strong elicitor of defense pathways.
2009-10-31 | GSE17193 | GEO
Project description:Chitosan has been widely used in food industry as a weight-loss aid and a cholesterol-lowering agent. Previous studies have shown that chitosan affects metabolic responses and contributes to anti-diabetic, hypocholestermic, and blood glucose-lowering effects; however, the in vivo targeting sites and mechanisms of chitosan remain to be clarified. In this study, we constructed transgenic mice which carried the luciferase genes driven by peroxisome proliferator-activated receptor (PPAR), a key regulator of fatty acid and glucose metabolism. Bioluminescent imaging of PPAR transgenic mice was applied to report the organs that chitosan acted on, and gene expression profiles of chitosan-targeted organs were further analyzed to elucidate the mechanisms of chitosan. Bioluminescent imaging showed that constitutive PPAR activities were detected in brain and gastrointestinal tract. Administration of chitosan significantly activated the PPAR activities in brain and stomach. Microarray analysis of brain and stomach showed that several pathways involved in lipid and glucose metabolism were regulated by chitosan. Moreover, the expression levels of metabolism-associated genes like apolipoprotein B (apoB) and ghrelin genes were down-regulated by chitosan. In conclusion, these findings suggested the feasibility of PPAR bioluminescent imaging-guided transcriptomic analysis on the evaluation of chitosan-affected metabolic responses in vivo. Moreover, we newly identified that downregulated expression of apoB and ghrelin genes were novel mechanisms for chitosan-affected metabolic responses in vivo . Mice (6 to 8 weeks old) were subcutaneously injected saline or 0.2 g/kg chitosan. Chitosan oligosaccharide lactate (MW=4000-6000, >90% deacetylation) was purchased from Sigma-Aldrich (St. Louis, MO, USA) and dissolved in DDW. For rosiglitazone treatment, mice were orally administered 50 mg/kg rosiglitazone. Mice were then imaged for the luciferase activity or sacrificed for microarray analysis at indicated periods.
2014-10-29 | E-GEOD-33565 | biostudies-arrayexpress
Project description:We treated Arabidopsis seedlings with chitosan and carried out a transcript profiling analysis (GeneChip microarrays) in order to identify genes and transcription factors regulated by chitosan. The results showed that jasmonate and defense responsive genes, camalexin and lignin biosynthetic genes were among genes up-regulated by chitosan. Several transcription factors are also strongly induced by chitosan. The results suggested that chitosan can be used as a strong elicitor of defense pathways. Experiment Overall Design: Arabidopsis thaliana, ecotype Columbia (Col-0) seeds were sterilized for 7 min in 1.7% (v/v) bleach solution, incubated over night in 4% PPM (Plant Preservative Mixture, Plant Cell Technology, Washington DC, USA) in a full strength sterilized Murashige-Skoog (MS) salt solution with gentle shaking. Subsequently, the seeds were rinsed in abundant sterile water and transferred into 2.5 ml liquid growing media (MS half strength solution) with 0.05% PPM in 6-well plates. The plates were incubated in the dark at 4 °C for two days and finally transferred to continuous light (90µm photons/ m-2) with gentle swirling for four days in a plant growth chamber at 22 °C. Experiment Overall Design: . Treatments were performed by comparing a control solution containing the solvent used to solubilize chitosan, and a chitosan solution concentrated 150 µg/ml.
2009-11-10 | E-GEOD-17193 | biostudies-arrayexpress
Project description:Chitosan has been widely used in food industry as a weight-loss aid and a cholesterol-lowering agent. Previous studies have shown that chitosan affects metabolic responses and contributes to anti-diabetic, hypocholestermic, and blood glucose-lowering effects; however, the in vivo targeting sites and mechanisms of chitosan remain to be clarified. In this study, we constructed transgenic mice which carried the luciferase genes driven by peroxisome proliferator-activated receptor (PPAR), a key regulator of fatty acid and glucose metabolism. Bioluminescent imaging of PPAR transgenic mice was applied to report the organs that chitosan acted on, and gene expression profiles of chitosan-targeted organs were further analyzed to elucidate the mechanisms of chitosan. Bioluminescent imaging showed that constitutive PPAR activities were detected in brain and gastrointestinal tract. Administration of chitosan significantly activated the PPAR activities in brain and stomach. Microarray analysis of brain and stomach showed that several pathways involved in lipid and glucose metabolism were regulated by chitosan. Moreover, the expression levels of metabolism-associated genes like apolipoprotein B (apoB) and ghrelin genes were down-regulated by chitosan. In conclusion, these findings suggested the feasibility of PPAR bioluminescent imaging-guided transcriptomic analysis on the evaluation of chitosan-affected metabolic responses in vivo. Moreover, we newly identified that downregulated expression of apoB and ghrelin genes were novel mechanisms for chitosan-affected metabolic responses in vivo .
2014-10-29 | GSE33565 | GEO
Project description:We studied the transcriptome changes in tomato against treatment with harpinPss, chitosan nanoparticles (CSNPs), and harpin loaded chitosan nanoparticles (H-CSNPs). We measured and compared the difference in transcript accumulation between treated- and control tomato leaves. Two independent experiments were performed at each time (24 h, 48 h and 72 h).
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