Short‐term Administration of Ethanol in Mice Deviates Antigen Presentation Activity Towards B Cells

Abstract

Alcohol has a variety of short‐ and long‐term effects on cell‐mediated and humoral immune response. Herein, we have characterized the impact of high‐dose EtOH administration on phenotypic and functional features of murine APC subsets, including dendritic cell (DC), macrophages and B cells. Impaired cytokine synthesis and Leishmania‐phagocytosis was observed in peritoneal macrophages following EtOH administration. Moreover, EtOH exposure led to decreased levels of splenic myeloid DC and increased percentage of macrophages with no changes in splenic lymphoid DC and B cells. Adverse effects of short‐term EtOH administration also resulted in impaired OVA‐endocytosis by DC and macrophages. In contrast, EtOH consumption upregulates OVA‐internalization by B cells. These changes on APC hierarchy may play a role shifting the fate of the immune response after EtOH ingestion. In addition to an overall downregulation of Toll‐like receptor‐TLR‐4 expression by splenic APC, a downregulation of TLR‐2 expression in macrophages was observed. Moreover, EtOH exposure altered the expression of co‐signalling molecules on splenic APC, downregulating CD40 on macrophages and upregulating CD80 on B cells, with no impact on DC subsets. The net result of changes in TLR‐mediated and co‐stimulatory signals may determine the altered immunological status induced by acute consumption of alcohol. A direct impact of high‐dose EtOH administration in the activation status of splenic CD4+ T cells was observed. Together, our results demonstrated that short‐term high‐dose EtOH administration has differential impact on APC populations, downregulating splenic macrophages and DC activity but up‐regulating B lymphocyte function as APC, and ultimately yielding a micro‐environment that led to increased activation of CD4+ T cells.

Previous Ingestion ofLactococcus lactisby Ethanol-Treated Mice Preserves Antigen Presentation Hierarchy in the Gut and Oral Tolerance Susceptibility

“…Previous studies from our group have demonstrated that short-term acute administration of EtOH might disturb the ability of developing OVA-oral tolerance by deviate the antigen presentation activity toward B cells (Andrade et al, 2009). Moreover, we have shown previously that this deviation in antigen presentation toward B cells led to an increased activation status of CD4 + T cells and this increase is associated with particular immune responses as detected by elevated IL-4 production and augmented levels of serum IgE.…”

“…Moreover, it has been suggested that the gastric compartment is also involved in this phenomenon, as allergic-type gastritis induced by acute short-term administration of EtOH impairs the establishment of oral tolerance mechanisms (Andrade et al, 2006). In fact, increasing evidences suggest that alcohol abuse lead to imbalanced immunomodulatory events, mainly impacting antigen presentation (Andrade et al, 2009;Heinz and Waltenbaugh, 2007).…”

“…Previous reports from our group demonstrated that high-dose ethanol (EtOH) administration is able to induce an allergic-type inflammatory response in function of enhanced levels of seric IgE, high levels of gastric interleukin (IL)-4 and increased IL-4 synthesis by splenic T cells after in vitro unspecific stimulus (concanavalin A) (Andrade et al, 2006(Andrade et al, , 2008(Andrade et al, , 2009). This allergic-type reaction in the GALT can disturb pathways involved in the establishment of regulatory mechanisms, hindering oral tolerance.…”

“…Previous studies have shown that EtOH treatment have differential impact on APCs, down-regulating DC and macrophage functions but up-regulating B-cell function, ultimately leading to increased activation of CD4 + T cells with high production of IL-4 (Andrade et al, 2009;D'Souza et al, 2013;Parlet and Schlueter, 2013).…”

Recent Insights Into the Role of Immune Cells in Alcoholic Liver Disease

“…TLR pathways are involved in the maturation and immunoglobulins synthesis of B cells. However, another study showed that short-term ethanol treatment at high dose down-regulated splenic macrophages and DCs activity via enhancing B cells function as the antigen-presenting cell, and eventually facilitating a microenvironment that leads to increased activation of CD4 + T cells (121). The roles of B cells within the spectrum of ALD deserve to be further elucidated with mechanistic studies required.…”