Immature myeloid cells (IMCs) increased in the peripheral blood of patients with alcohol use disorder (AUD) suppress the bactericidal activity of monocytes

Abstract

Abstract AUD patients have an increased risk of serious opportunistic infections. IMCs have been described as suppressor cells for host antibacterial defenses. In this study, IMCs isolated from AUD patients were examined for their inhibitory functions on the bactericidal activity of healthy donor (HD) monocytes. IMCs and monocytes were isolated from the peripheral blood of 10 AUD patients admitted to Osaka Medical Collage and 5 HD. HD monocytes (1 × 105 cells/ml) were stimulated with heat-killed Enterococcus faecalis, then cultured in media supplemented with the conditioned media of patient IMCs (24 hr-culture fluids, 10% v/v, 1 × 106 cells/ml). Twenty-four hrs after the cultivation, monocytes were harvested and tested for their bactericidal activities against E. faecalis. In some cases, patient IMCs, cultured with 5 μg/ml of retinoic acid (RA) for 24 hrs, were utilized for the experiments. Also, both groups of IMCs were analyzed for RA receptor (RAR) expression by flow cytometry. In the results, as compared to HD peripheral blood IMCs, the numbers of IMCs increased in AUD patients. HD monocytes were shown to be bactericidal against E. faecalis. However, the bactericidal activity of HD monocytes was not demonstrated when they were cultured with media supplemented with the conditioned media of patient IMCs. HD IMCs differentiated to monocytes or dendritic cells after cultivation with RA. However, AUD patient IMCs were shown to be not susceptible to RA treatment (patient IMCs, RAR−; HD IMCs, RAR+). These results suggest that, through the production of some soluble factors active against killing functions of monocytes, patient IMCs increase the susceptibility of AUD patients to opportunistic infections.