Comprehensive analysis of serum and innate immune cells revealed age-related alternations

Age-related alterations in immunity have been linked to increased incidence of infections and decreased responses to vaccines in the aging population. These immune dysfunctions, termed immunosenescence, have been linked to the intricate interactions between the innate and adaptive immune responses. The impact of aging on innate immunity remains an open question. We performed a comprehensive analysis of serum and peripheral blood mononuclear cells (PMBCs) isolated from healthy non-frail adults (≤ 40 years) and old individuals (≥ 65 years). The basal level of circulating inflammatory cytokines and chemokines were measured, as well as transcriptome data was analyzed for both ex vivo and agonist stimulated DCs and monocyte subsets. We observed that sorted DC (BDCA-1, -2, and -3) and monocyte (CD14 + CD16 − ,CD14 dim CD16 + , and CD14 + CD16 + ) subsets were primarily distinct and have unique transcriptional profiles. Under ex vivo conditions, innate subsets did not reveal significant age-related alternations; however, agonist stimulated-monocytes from adults and old subjects did show differences at the transcriptional and functional levels. After stimulation of TLR4 (LPS), TLR7/8 (CLO97), and RIGI (5′-pppRNA), we observed higher production of interferons, CCL8, CCL20, and IL1B in monocytes isolated from adults compared to old individuals. Pathway analysis revealed that innate agonists induced functional pathways in monocytes isolated from both adults and old subjects. Overall, our data reveals a wide range of potential age-associated alternations in pattern recognition receptors (PRRs) signaling and have implications for strategies to enhance the immune response in the context of infection or immunization.