Effects of ageing and frailty on circulating monocyte and dendritic cell subsets

Ageing is associated with dysregulated immune responses, resulting in impaired resilience against infections and a low-grade inflammation known as inflammageing. Frailty is a measurable condition in older adults characterized by decreased health and physical impairment. Dendritic cells (DCs) and monocytes play a crucial role in initiating and steering immune responses. To assess whether their frequencies and phenotypes in the blood are affected by ageing or frailty, we performed a flow cytometry study (14 markers) on monocyte and DC subsets in an immune ageing cohort (SENEX). Participants were divided into three groups (n=15 each): healthy young controls (HYC, median age 29 years), healthy older controls (HOC, 73 years) and Frail older controls (76 years). Frailty status was based on Tilburg Frailty Index scores. Among HLA-DR+/CD19-cells, monocyte subsets (classical, intermediate, non-classical) were identified by CD14 and CD16 expression, and DC subsets (conventional (c)DC1, cDC2, plasmacytoid (p)DC) by CD11c, CD1c, CD141 and CD303 expression. Using unsupervised and conventional gating strategies, we observed a substantially lower proportion of pDCs in the HOC compared to the HYC. Additionally, we observed higher expression of activation markers on classical and intermediate monocytes and on cDC2 in HOC compared to HYC. Comparing the Frail to the age-matched HOC group, we observed only one important difference: a higher expression of CD40 on classical and non-classical monocytes in Frail individuals. In this cross-sectional study, we document a substantial effect of ageing on monocytes and DCs. The reduction of pDCs in older people may underly their impaired ability to counter viral infections, whereas the enhanced expression of activation markers could indicate a state of inflammageing. Future studies could elucidate the functional consequences of CD40 upregulation with frailty.