Fetal/neonatal ethanol exposure irreversibly alters dendritic cell function in adult mice

Abstract

Children born to alcoholic mothers are known to have increased incidence and severity of infections.We have developed a model of fetal/neonatal alcohol exposure (FAE) in which female mice are maintained on 10% EtOH in the drinking water during breeding and gestation, and then on 12% EtOH during lactation.Pups have successfully been weaned and showed no significant difference in weights from controls through 12 weeks of age.These pups have been studied at 20 d (weaning) and 12 weeks (young adult) for DC function.Splenic DC numbers did not change. FAE decreased the ability of these DC to stimulate allogeneic T cells,changes that persisted following cessation of EtOH exposure.In addition, antigen‐specific Foxp3+ regulatory T cells were induced following antigen presentation by FAE DC at a higher rate than by control DC. IL‐10 production by OTII T cells increased and IL‐2 production decreased following stimulation with OVA peptide‐pulsed FAE DC relative to control DC.These results indicate that mice born to EtOH‐consuming mothers have deficiencies in DC function that are persistent following cessation of EtOH exposure, and provide a mechanism, which could at least partially explain the increased incidence and severity of infection in children of alcoholic mothers.