Investigation of sex-based differences in the immunotoxicity of silver nanoparticles

Abstract

The growing application of silver nanoparticles (AgNPs) in consumer, healthcare, and industrial products has raised concern over potential health implications due to increasing exposure. The evaluation of the immune response to nanomaterials is one of the key criteria to assess their biocompatibility. There are well-recognized sex-based differences in innate and adaptive immune responses. However, there is limited information available using human models. The aim was to investigate the potential sex-based differences in immune functions after exposure to AgNPs using human peripheral blood mononuclear cells (PBMCs) and plasma from healthy donors. These functions include inflammasome activation, cytokine expression, leukocyte proliferation, chemotaxis, plasma coagulation, and complement activation. AgNPs were characterized by dynamic light scattering and transmission electron microscopy. Inflammasome activation by AgNPs was measured after 6- and 24-hours incubations. AgNPs-induced inflammasome activation was significantly higher in the females, especially for the 6-hour exposure. No sex-based differences were observed for Ag ions controls. Younger donors exhibited significantly more inflammasome activation than older donors after 24-hours exposure. IL-10 was significantly suppressed in males and females after exposure. AgNPs suppressed leukocyte proliferation similarly in males and females. No chemoattractant effects, no alterations in plasma coagulation, or activation of the complement were observed after AgNPs exposure. In conclusion, the results highlight that there are distinct sex-based differences in inflammasome activation after exposure to AgNPs in human PBMCs. The results highlight the importance of considering sex-based differences in inflammasome activation induced by exposure to AgNPs in any future biocompatibility assessment for products containing AgNPs.

Keywords:

• Inflammasome
• immunotoxicity
• silver nanoparticles
• sex-based difference
• peripheral blood mononuclear cells

Acknowledgments

Anil Patri PhD for the shared access to the equipment from the NCTR Nanotechnology Core Facility. Alena Savenka and Austin Hall for technical support with electron microscopy.

Authors’ contributions

Bandon Canup: Investigation, methodology, formal analysis, visualization, writing-original draft. Paul Roger: Formal statistical analysis, review & editing. Angel Paredes: Electron microscopy investigations. Wimolnut Manheng: Regulatory and scientific guidance, review & editing. Beverly Lyn-Cook: Scientific guidance, review & editing. Tariq Fahmi: conceptualization, methodology, analysis, supervision, project administration, writing, review & editing. All authors have read and agreed to the final version of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

Data will be available upon an official request.

Additional information

Funding

This work was supported by the FDA Office of Women’s Health. This project was supported in part by an appointment to the ORISE Research Participation Program at the National Center for Toxicological Research (NCTR), U.S. Food and Drug Administration, administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and FDA/NCTR.