Pulmonary delivery of silver nanoparticles prevents influenza infection by recruiting and activating lymphoid cells

• Published in: Biomaterials 2025-01, Vol.312, p.122721, Article 122721
• Main Authors: Martín-Faivre, Lydie, Prince, Lisa, Cornu, Clémentine, Villeret, Bérengère, Sanchez-Guzman, Daniel, Rouzet, François, Sallenave, Jean-Michel, Garcia-Verdugo, Ignacio
• Format: Article
• Language: English
• Subjects: Alveolar macrophages; Animals; Antiviral Agents - pharmacology; Antiviral Agents - therapeutic use; Female; Influenza infection; Influenza prevention; Killer Cells, Natural - drug effects; Lung - drug effects; Lung - pathology; Lung - virology; Lung delivery; Lymphocyte Activation - drug effects; Lymphocytes - drug effects; Lymphocytes - metabolism; Lymphoid cells; Macrophages, Alveolar - drug effects; Macrophages, Alveolar - metabolism; Macrophages, Alveolar - virology; Metal Nanoparticles - chemistry; Mice; Mice, Inbred C57BL; Orthomyxoviridae Infections - drug therapy; Orthomyxoviridae Infections - prevention & control; Orthomyxoviridae Infections - virology; Silver - chemistry; Silver - pharmacology; Silver nanoparticles
• ISSN: 0142-9612; 1878-5905; 1878-5905
• DOI: 10.1016/j.biomaterials.2024.122721

Silver nanoparticles (AgNPs) are a potential antiviral agent due to their ability to disrupt the viral particle or alter the virus metabolism inside the host cell. In vitro, AgNPs exhibit antiviral activity against the most common human respiratory viruses. However, their capacity to modulate immune responses during respiratory viral infections has yet to be explored. This study demonstrates that administering AgNPs directly into the lungs prior to infection can reduce viral loads and therefore virus-induced cytokines in mice infected with influenza virus or murine pneumonia virus. The prophylactic effect was diminished in mice with depleted lymphoid cells. We showed that AgNPs-treatment resulted in the recruitment and activation of lymphocytes in the lungs, particularly natural killer (NK) cells. Mechanistically, AgNPs enhanced the ability of alveolar macrophages to promote both NK cell migration and IFN-γ production. By contrast, following infection, in mice treated with AgNPs, NK cells exhibited decreased activation, indicating that these nanoparticles can regulate the potentially deleterious activation of these cells. Overall, the data suggest that AgNPs may possess prophylactic antiviral properties by recruiting and controlling the activation of lymphoid cells through interaction with alveolar macrophages.