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
- young adults
- physical activity
- regulatory t cells
- innate immune
- high glucose
- induced apoptosis
- binding protein
- diabetic rats
- signaling pathway
- middle aged
- drug induced
- poor prognosis
- respiratory syndrome coronavirus
- cell cycle arrest
- protein kinase
- electronic health record
- case report
- cell proliferation
- toll like receptor
- inflammatory response
- fatty acid
- endoplasmic reticulum stress
- cell death
- long non coding rna