Adenosine accumulation in the blood of newborn mice weakens antimicrobial host defenses

• DOI: 10.1093/jleuko/qiaf003
• Publication Date: 2025-01-18T00:01:04Z
• Authors: Carola Ledderose; Eleftheria-Angeli...; Mark Elevado; Ava Stevenson; Reem Abutabikh; Julian Curatolo; Wolfgang G Junger

Pediatric intensive care patients are particularly susceptible to severe bacterial infections because of ineffective neutrophil responses. The reasons why neutrophils newborns less responsive than those adults not clear. Because adenosine triphosphate (ATP) and (ADO) tightly regulate neutrophils, we studied whether the ATP ADO levels in blood newborn mice could impair function their neutrophils. We observed significant changes plasma throughout lifespan mice. were significantly higher older mice, while lower. These striking juvenile with about 80 600 nM versus 130 190 juveniles, respectively. ratios (with 0.2) lower juveniles (1.4) (0.5). low ATP/ADO correlated weakened activation responses following vitro stimulation a formyl peptide receptor agonist markedly morbidity mortality rate infection. found that enhanced AMP hydrolysis via CD73, lack breakdown by deaminase, reduced uptake nucleoside transporters responsible for conclude extracellular accumulation impairs inflammatory reduces ability mount effective antimicrobial defenses against infections.