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

Abstract

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.

Lack of strong innate immune reactivity renders macrophages alone unable to control productive Varicella-Zoster Virus infection in an isogenic human iPSC-derived neuronal co-culture model

“…Although several groups have studied VZV infection in peripheral blood mononuclear cells (PBMCs) and subsets of PBMCs before (17-21), few have focused on monocytes and macrophages in particular (3,4). Kennedy demonstrated the permissiveness of monocytes to productive VZV infection (4) and several other groups described innate immune activation in monocytes following VZV infection in both experimental and clinical observations (22)(23)(24). The contribution of macrophages to the innate immune response against a neuronal VZV infection however requires further investigation.…”