“Just right” combinations of adjuvants with nanoscale carriers activate aged dendritic cells without overt inflammation
Abstract Background The loss in age-related immunological markers, known as immunosenescence, is caused by a combination of factors, one of which is inflammaging. Inflammaging is associated with the continuous basal generation of proinflammatory cytokines. Studies have demonstrated that inflammaging...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-03-01
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| Series: | Immunity & Ageing |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12979-023-00332-0 |
| _version_ | 1797863536044539904 |
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| author | Ananya Ananya Kaitlyn G. Holden Zhiling Gu Dan Nettleton Surya K. Mallapragada Michael J. Wannemuehler Marian L. Kohut Balaji Narasimhan |
| author_facet | Ananya Ananya Kaitlyn G. Holden Zhiling Gu Dan Nettleton Surya K. Mallapragada Michael J. Wannemuehler Marian L. Kohut Balaji Narasimhan |
| author_sort | Ananya Ananya |
| collection | DOAJ |
| description | Abstract Background The loss in age-related immunological markers, known as immunosenescence, is caused by a combination of factors, one of which is inflammaging. Inflammaging is associated with the continuous basal generation of proinflammatory cytokines. Studies have demonstrated that inflammaging reduces the effectiveness of vaccines. Strategies aimed at modifying baseline inflammation are being developed to improve vaccination responses in older adults. Dendritic cells have attracted attention as an age-specific target because of their significance in immunization as antigen presenting cells that stimulate T lymphocytes. Results In this study, bone marrow derived dendritic cells (BMDCs) were generated from aged mice and used to investigate the effects of combinations of adjuvants, including Toll-like receptor, NOD2, and STING agonists with polyanhydride nanoparticles and pentablock copolymer micelles under in vitro conditions. Cellular stimulation was characterized via expression of costimulatory molecules, T cell-activating cytokines, proinflammatory cytokines, and chemokines. Our results indicate that multiple TLR agonists substantially increase costimulatory molecule expression and cytokines associated with T cell activation and inflammation in culture. In contrast, NOD2 and STING agonists had only a moderate effect on BMDC activation, while nanoparticles and micelles had no effect by themselves. However, when nanoparticles and micelles were combined with a TLR9 agonist, a reduction in the production of proinflammatory cytokines was observed while maintaining increased production of T cell activating cytokines and enhancing cell surface marker expression. Additionally, combining nanoparticles and micelles with a STING agonist resulted in a synergistic impact on the upregulation of costimulatory molecules and an increase in cytokine secretion from BMDCs linked with T cell activation without excessive secretion of proinflammatory cytokines. Conclusions These studies provide new insights into rational adjuvant selection for vaccines for older adults. Combining appropriate adjuvants with nanoparticles and micelles may lead to balanced immune activation characterized by low inflammation, setting the stage for designing next generation vaccines that can induce mucosal immunity in older adults. |
| first_indexed | 2024-04-09T22:37:03Z |
| format | Article |
| id | doaj.art-609d2ca05bc844b4b267bacf27de1c3c |
| institution | Directory Open Access Journal |
| issn | 1742-4933 |
| language | English |
| last_indexed | 2024-04-09T22:37:03Z |
| publishDate | 2023-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Immunity & Ageing |
| spelling | doaj.art-609d2ca05bc844b4b267bacf27de1c3c2023-03-22T12:22:48ZengBMCImmunity & Ageing1742-49332023-03-0120111610.1186/s12979-023-00332-0“Just right” combinations of adjuvants with nanoscale carriers activate aged dendritic cells without overt inflammationAnanya Ananya0Kaitlyn G. Holden1Zhiling Gu2Dan Nettleton3Surya K. Mallapragada4Michael J. Wannemuehler5Marian L. Kohut6Balaji Narasimhan7Nanovaccine Institute, Iowa State UniversityNanovaccine Institute, Iowa State UniversityDepartment of Statistics, Iowa State UniversityDepartment of Statistics, Iowa State UniversityNanovaccine Institute, Iowa State UniversityNanovaccine Institute, Iowa State UniversityNanovaccine Institute, Iowa State UniversityNanovaccine Institute, Iowa State UniversityAbstract Background The loss in age-related immunological markers, known as immunosenescence, is caused by a combination of factors, one of which is inflammaging. Inflammaging is associated with the continuous basal generation of proinflammatory cytokines. Studies have demonstrated that inflammaging reduces the effectiveness of vaccines. Strategies aimed at modifying baseline inflammation are being developed to improve vaccination responses in older adults. Dendritic cells have attracted attention as an age-specific target because of their significance in immunization as antigen presenting cells that stimulate T lymphocytes. Results In this study, bone marrow derived dendritic cells (BMDCs) were generated from aged mice and used to investigate the effects of combinations of adjuvants, including Toll-like receptor, NOD2, and STING agonists with polyanhydride nanoparticles and pentablock copolymer micelles under in vitro conditions. Cellular stimulation was characterized via expression of costimulatory molecules, T cell-activating cytokines, proinflammatory cytokines, and chemokines. Our results indicate that multiple TLR agonists substantially increase costimulatory molecule expression and cytokines associated with T cell activation and inflammation in culture. In contrast, NOD2 and STING agonists had only a moderate effect on BMDC activation, while nanoparticles and micelles had no effect by themselves. However, when nanoparticles and micelles were combined with a TLR9 agonist, a reduction in the production of proinflammatory cytokines was observed while maintaining increased production of T cell activating cytokines and enhancing cell surface marker expression. Additionally, combining nanoparticles and micelles with a STING agonist resulted in a synergistic impact on the upregulation of costimulatory molecules and an increase in cytokine secretion from BMDCs linked with T cell activation without excessive secretion of proinflammatory cytokines. Conclusions These studies provide new insights into rational adjuvant selection for vaccines for older adults. Combining appropriate adjuvants with nanoparticles and micelles may lead to balanced immune activation characterized by low inflammation, setting the stage for designing next generation vaccines that can induce mucosal immunity in older adults.https://doi.org/10.1186/s12979-023-00332-0ImmunosenescenceInflammationDendritic cellsVaccinesPattern recognition receptorsNanoparticles |
| spellingShingle | Ananya Ananya Kaitlyn G. Holden Zhiling Gu Dan Nettleton Surya K. Mallapragada Michael J. Wannemuehler Marian L. Kohut Balaji Narasimhan “Just right” combinations of adjuvants with nanoscale carriers activate aged dendritic cells without overt inflammation Immunity & Ageing Immunosenescence Inflammation Dendritic cells Vaccines Pattern recognition receptors Nanoparticles |
| title | “Just right” combinations of adjuvants with nanoscale carriers activate aged dendritic cells without overt inflammation |
| title_full | “Just right” combinations of adjuvants with nanoscale carriers activate aged dendritic cells without overt inflammation |
| title_fullStr | “Just right” combinations of adjuvants with nanoscale carriers activate aged dendritic cells without overt inflammation |
| title_full_unstemmed | “Just right” combinations of adjuvants with nanoscale carriers activate aged dendritic cells without overt inflammation |
| title_short | “Just right” combinations of adjuvants with nanoscale carriers activate aged dendritic cells without overt inflammation |
| title_sort | just right combinations of adjuvants with nanoscale carriers activate aged dendritic cells without overt inflammation |
| topic | Immunosenescence Inflammation Dendritic cells Vaccines Pattern recognition receptors Nanoparticles |
| url | https://doi.org/10.1186/s12979-023-00332-0 |
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