Chronic alcohol consumption induces peripheral skewed dentritic cell sets without affecting dendritic cell progenitors. (HEM5P.238)

Abstract

Abstract Alcoholism impairs innate and adaptive immune responses and increases susceptibility to infectious diseases, caused among others by alcohol induced defects in dendritic cell (DC) function and frequency. This study aims at understanding how DC turnover is affected by chronic alcohol exposure, characterizing its influence on DC development at the progenitor stages and the underlying mechanisms. Alcohol (EtOH) is delivered in the drinking water to C57BL/6 mice at 20% v/v (Meadows-Cook diet). Lymphoid tissue (LT) DCs from thymus and spleen, non-lymphoid tissue (NLT) DCs from liver and lung and bone marrow (BM) progenitors are analyzed by flow cytometry. After 12 weeks of EtOH exposure BM populations at the Macrophage-DC Progenitor (MDP) stage decrease by 60% (P<0,05) but there is no difference in the numbers of Common DC Progenitors (CDP). In the liver we observe a 70% increase (P<0,05) of plasmacytoid DCs (pDC) while CD103+ classic DCs (cDC) decrease by 50% (P<0,01). Concordantly hepatic T cell numbers decrease: CD8+ CTL by 40% (P<0,01), CD4+ TH by 30% (P<0,005) and CD4+ TREG by 45% (P<0,05). In summary, alcohol in a chronic model does not change CDP numbers, the main progenitor of pDC and cDC, suggesting little effect on DC development. There is however a major imbalance between pDC and cDC, reflected by the impact on steady-state T cell subsets. Going forward we will elucidate the underlying mechanisms responsible for this peripheral effect of alcohol on DC populations.