Age-dependent changes in phagocytic activity: in vivo response of mouse pulmonary antigen presenting cells to direct lung delivery of charged PEGDA nanoparticles
Date
2024-08-12
Journal Title
Journal ISSN
Volume Title
Publisher
Journal of Nanobiotechnology
Abstract
Background
Current needle-based vaccination for respiratory viruses is ineffective at producing sufficient, long-lasting local immunity in the elderly. Direct pulmonary delivery to the resident local pulmonary immune cells can create long-term mucosal responses. However, criteria for drug vehicle design rules that can overcome age-specific changes in immune cell functions have yet to be established.
Results
Here, in vivo charge-based nanoparticle (NP) uptake was compared in mice of two age groups (2- and 16-months) within the four notable pulmonary antigen presenting cell (APC) populations: alveolar macrophages (AM), interstitial macrophages (IM), CD103+ dendritic cells (DCs), and CD11b+ DCs. Both macrophage populations exhibited preferential uptake of anionic nanoparticles but showed inverse rates of phagocytosis between the AM and IM populations across age. DC populations demonstrated preferential uptake of cationic nanoparticles, which remarkably did not significantly change in the aged group. Further characterization of cell phenotypes post-NP internalization demonstrated unique surface marker expression and activation levels for each APC population, showcasing heightened DC inflammatory response to NP delivery in the aged group.
Conclusion
The age of mice demonstrated significant preferences in the charge-based NP uptake in APCs that differed greatly between macrophages and DCs. Carefully balance of the targeting and activation of specific types of pulmonary APCs will be critical to produce efficient, age-based vaccines for the growing elderly population.
Description
This article was originally published in Journal of Nanobiotechnology. The version of record is available at: https://doi.org/10.1186/s12951-024-02743-7. © The Author(s) 2024.
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
Keywords
aging, phagocytosis, antigen presenting cells, pulmonary delivery, pulmonary immunity, nanoparticles
Citation
Sudduth, E.R., López Ruiz, A., Trautmann-Rodriguez, M. et al. Age-dependent changes in phagocytic activity: in vivo response of mouse pulmonary antigen presenting cells to direct lung delivery of charged PEGDA nanoparticles. J Nanobiotechnol 22, 476 (2024). https://doi.org/10.1186/s12951-024-02743-7