Lipid nanoparticles (LNP) induce activation and maturation of antigen presenting cells in young and aged individuals.
Jennifer ConnorsDavid JoynerNathan J MegeGina M CusimanoMatthew R BellJennifer MarcyBhavani TaramangalamKenneth M KimPaulo J C LinYing K TamDrew WeissmanMichele A KutzlerMohamad-Gabriel AlamehElias K HaddadPublished in: Communications biology (2023)
Herein, we studied the impact of empty LNP (eLNP), component of mRNA-based vaccine, on anti-viral pathways and immune function of cells from young and aged individuals. eLNP induced maturation of monocyte derived dendritic cells (MDDCs). We further show that eLNP upregulated CD40 and induced cytokine production in multiple DC subsets and monocytes. This coincided with phosphorylation of TANK binding kinase 1 (pTBK1) and interferon response factor 7 (pIRF7). In response to eLNP, healthy older adults (>65 yrs) have decreased CD40 expression, and IFN-γ output compared to young adults (<65 yrs). Additionally, cells from older adults have a dysregulated anti-viral signaling response to eLNP stimulation, measured by the defect in type I IFN production, and phagocytosis. Overall, our data show function of eLNP in eliciting DC maturation and innate immune signaling pathways that is impaired in older adults resulting in lower immune responses to SARS-CoV-2 mRNA-based vaccines.
Keyphrases
- dendritic cells
- sars cov
- immune response
- physical activity
- regulatory t cells
- young adults
- high glucose
- innate immune
- binding protein
- induced apoptosis
- diabetic rats
- signaling pathway
- poor prognosis
- drug induced
- cell cycle arrest
- middle aged
- protein kinase
- electronic health record
- pi k akt
- endothelial cells
- cell proliferation
- cell death
- toll like receptor
- epithelial mesenchymal transition
- deep learning
- artificial intelligence
- transcription factor