Zoledronate rescues immunosuppressed monocytes in sepsis patients.

Zoledronate rescues immunosuppressed monocytes in sepsis patients. Immunology. 2019 Oct 13;: Authors: Raffray L, Burton RJ, Baker SE, Morgan MP, Eberl M Abstract Severe sepsis is often accompanied by a transient immune paralysis, which is associated with enhanced susceptibility to secondary infections and poor clinical outcomes. The functional impairment of antigen-presenting cells is considered to be a major hallmark of this septic immunosuppression, with reduced HLA-DR expression on circulating monocytes serving as predictor of mortality. Unconventional lymphocytes like γδ T cells have the potential to restore immune defects in a variety of pathologies including cancer but their use to rescue sepsis-induced immunosuppression has not been investigated. Our own previous work showed that Vγ9/Vδ2+ γδ T cells are potent activators of monocytes from healthy volunteers in vitro, and in individuals with osteoporosis after first-time administration of the anti-bone resorption drug zoledronate in vivo. We show here that zoledronate readily induces upregulation of HLA-DR, CD40 and CD64 on monocytes from both healthy controls and sepsis patients, which could be abrogated by neutralising the pro-inflammatory cytokines IFN-γ and TNF-α in the cultures. In healthy controls, the upregulation of HLA-DR on monocytes was proportional to the baseline percentage of Vγ9/Vδ2 T cells in the PBMC population. Of note, a proportion of sepsis patient...
Source: Immunology - Category: Allergy & Immunology Authors: Tags: Immunology Source Type: research