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Study of the effects of nanoparticles on the immune system

Abstract : The unique characteristics of nanomaterials (NMs) are valuable in many industrial and biomedical applications. However, NMs might also give rise to unforeseen toxicity that could adversely affect the biological system specially the immune system. In the immune system as phagocytes can engulf foreign materials therefore they are appropriate for immunotoxicity screening because these cells participate in unspecific and specific immune responses. In this study, we investigated the impact of different NMs, such as gold nanoparticles (AuNPs), neutral lipid nanoparticles (NLCs), cationic lipid nanoparticles (CLCs), and amphiphilic dendrimers (ADs) on primary macrophages (BMDMs) and dendritic cells (BMDCs) by two approaches. In the first approach, we investigated the direct effect of exposure to NMs. In the second approach, we studied the indirect effect by activating the NMs exposed cells with different activators (LPS and IL-4). The study of direct effect of NMs shows that none of the tested NMs altered the phagocytosis capacity. All of the NMs had none or little direct effect on BMDCs activation. In case of BMDMs, AuNPs, CLCs, and ADs significantly decreased cell activation while NLCs did not. The study of cytokine production based on IL-6 and TNF- production, NO production, and cellular metabolism based on the investigation of glycolysis and mitochondrial metabolism also indicated no or little direct effect on BMDCs and BMDMs. However, we have noticed a significant increase in MCP-1 production by CLCs and ADs exposed cells while AuNPs and NLCs did not modulate MCP-1 production. Also, we noted that CLCs and NLCs at high concentrations could slightly increase ROS production while AuNPs and ADs did not modulate ROS production by BMDMs and BMDCs. Investigation of indirect effect of NMs revealed, when NMs exposed cells were challenged with LPS, we have recorded NMs specific modulation in the response of BMDCs based on cell activation, cytokine and chemokine secretion, NO, and ROS production. All NMs showed none or little modification of cellular metabolism of BMDCs. On the other hand, we have recorded a significant alteration in NMs exposed BMDMs upon LPS challenge in response to cell activation, cytokine and chemokine secretion, NO production, and cellular metabolism. However, ROS production remains unaltered in the case of all the NMs exposed BMDMs. The study of in vitro antigen presentation, revealed that exposure to different NMs altered T cell-specific cytokines reflecting alteration in CD4 + T lymphocytes polarization. Overall, these results demonstrate that NMs directly do not modify phagocytic activity, cytokine and chemokine production, NO and ROS production, cellular metabolism, but when instigated with an activation signal like LPS or IL-4, NMs exposed cells respond differently. The outcome of this study enriches the knowledge regarding NMs specific immunotoxicity, which may facilitate the design of nanomaterials that retain their useful properties, but display reduced toxicity (i.e., safety-by-design). This research will also improve our understanding of how different NMs can modulate the immune system, which might help suggest new therapy acting on the immune system such as antiinflammatory drugs or vaccines.
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https://www.hal.inserm.fr/tel-03374657
Contributor : Patrice Marche Connect in order to contact the contributor
Submitted on : Tuesday, October 12, 2021 - 11:36:47 AM
Last modification on : Thursday, October 14, 2021 - 3:24:03 AM

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  • HAL Id : tel-03374657, version 1

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Arindam K Dey. Study of the effects of nanoparticles on the immune system. Life Sciences [q-bio]. Université Grenoble Alpes, 2020. English. ⟨tel-03374657⟩

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