The frequency of interleukin‐1β‐producing monocytes is significantly associated with varicella‐zoster responses of nursing home residents

Summary Previous studies have demonstrated that the status of the T cell compartment and inflammation‐related factors are associated with the immunogenicity of the varicella‐zoster virus (VZV) vaccine in older adults; however, little is known about the roles of other immune cell subsets known to influence the generation and maintenance of immunological memory. Responses to a live‐attenuated VZV vaccine were studied in relation to peripheral blood mononuclear cell (PBMC) composition and function in a sample of 30 nursing home residents (aged 80–99 years). Interferon‐gamma enzyme‐linked immunospot (ELISPOT) was used to measure VZV responses at baseline and 6 weeks following vaccination, and associations were sought with the frequencies of monocytes and T, B and natural killer (NK) cells and the production and secretion of cytokines following their ex‐vivo stimulation with different agents. While only the frequency of interleukin (IL)‐6 + CD14 + monocytes was inversely associated with post‐vaccination VZV response, amounts of IL‐1β, IL‐10, IL‐17A and tumour necrosis factor (TNF) secreted by PBMCs and the frequency of IL‐1β + CD14 + monocytes was positively correlated with pre‐vaccination VZV response. Furthermore, both bivariate correlation and causal mediation analyses supported the notion that IL‐1β + CD14 + monocytes were significant mediators of the associations between IL‐1β and TNF secretion by PBMCs and pre‐vaccination VZV responses. Our findings implicate a strong cytokine response mediated by inflammatory IL‐1β + monocytes in coordinating responses of long‐lived VZV‐reactive memory T cells, but with an opposing effect of IL‐6 + CD14 + monocytes. Whether monocyte status promotes or inhibits the induction and/or maintenance of these memory T cells later in life has yet to be determined.