Abstract

Gold nanoparticles (AuNPs) have demonstrated outstanding performance in many biomedical applications. Their safety is recognised; however, their effects on the immune system remain ill defined. Antigen-presenting cells (APCs) are immune cells specialised in sensing external stimulus and in capturing exogenous materials then delivering signals for the immune responses. We used primary macrophages (Ms) and dendritic cells (DCs) of mice as an APC model. Whereas AuNPs did not alter significantly Ms and DCs functions, the exposure to AuNPs affected differently Ms and DCs in their responses to subsequent stimulations. The secretion of inflammatory molecules like cytokines (IL-6, TNF-α), chemokine (MCP-1), and reactive oxygen species (ROS) were altered differently in Ms and DCs. Furthermore, the metabolic activity of Ms was affected with the increase of mitochondrial respiration and glycolysis, while only a minor effect was seen on DCs. Antigen presentation to T cells increased when DCs were exposed to AuNPs leading to stronger Th1, Th2, and Th17 responses. In conclusion, our data provide new insights into the complexity of the effects of AuNPs on the immune system. Although AuNPs may be considered as devoid of significant effect, they may induce discrete modifications on some functions that can differ among the immune cells.

Highlights

  • In the past few decades, nanoparticles (NPs) have been introduced in medicine for therapeutic and diagnostic applications

  • As expected after the activation of Antigen-presenting cells (APCs) by LPS, the number of activated cells expressing both CD86 and major histocompatibility complex (MHC-II) increased from 27.57% to 74.97% for BMDCs (Figure 4A), but a negligible change was observed in the case of bone marrow-derived macrophages (BMDMs) (18.43 to 14.69%) (Figure 4B)

  • AuNPs are widely used in targeted drug delivery, c their ability to target specific cells followed by their internalisation

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Summary

Introduction

In the past few decades, nanoparticles (NPs) have been introduced in medicine for therapeutic and diagnostic applications. Upon activation by a foreign pathogen, DCs secrete a large range of cytokines, implicated in the activation of natural killers or the control of T cell response, for example [8] The integrity of both these cell populations is necessary to ensure proper responses to infection; they are, likely the most relevant experimental models for the study of the effects of NPs on cell fate. Both DCs and Ms express toll-like receptors (TLR) that allow them to detect and respond to pathogen-derived molecules [9]. We evaluated the effect of AuNPs on the following: (1) phagocytic capacity of Ms and DCs; (2) cell activation; (3) cytokine production; (4) redox profile; (5) metabolic profile, and (6) LT activation by DCs

Cell Culture
Incubation with AuNPs
Toxicity Assessment
Phagocytosis Assay
Cell Activation
Cytokine Immunoassays
The NO and ROS Production
2.10. Metabolic Flux Analysis
2.11. Antigen Presentation Assay
2.12. Statistical Analysis
3.3.Results
Phagocytosis Capacity of Macrophages
Phagocytosis
(Supplementary
The AuNPs Do Not Modify the Secretions of Signalling Factors by APCs
Analysis of the Mitochondrial Metabolism of APCs
Analysis of the Glycolysis of APCs
Glycolysis ofactivated
Discussion

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