Ethanol consumption modifies dendritic cell antigen presentation in mice.
BACKGROUND
Alcohol consumption impairs type 1 cell-mediated adaptive immune responses both in vivo and in vitro. The present study investigated the effect of alcohol consumption on antigen-presenting cell (APC) populations and cytokine production.


METHODS
BALB/c were fed ethanol-containing, pair-fed isocaloric liquid control, or solid diets for 11 days. Macrophage and dendritic cell (DC) populations were isolated by paramagenetic bead separation and used to present ovalbumin (OVA) to highly purified syngeneic CD4+ T cells derived from DO11.10 T cell receptor transgenic mice in coculture. DC isolated from diet-fed mice were also used to present OVA to highly purified CD4+ T cells derived from antigen-naïve DO11.10Rag2-/- mice that are devoid of memory T cells. In vitro cytokine responses, interleukin (IL) -2, IL-6, IL-12, IL-13, IL-17A, and interferon-gamma (IFN-gamma) were measured by enzyme-linked immunosorbent assay. Flow cytometry measured cell surface molecule expression.


RESULTS
Alcohol consumption impairs delayed hypersensitivity responses (type 1) and enhances serum IgE levels (type 2). CD11c+ DC, but not F4/80+ macrophages, support cytokine responses by purified CD4+ T cells. CD11c+ DC derived from ethanol consuming BALB/c mice show diminished ability to support IFN-gamma responses by purified CD4+ T cells derived from DO11.10 or DO11.10Rag2-/- mice. Subset analysis indicates that of the 3 "conventional" DC subsets found in mouse spleens, CD11c+CD8(alpha)+ DCs are both responsible for OVA presentation and susceptible to the effects of ethanol. Ethanol consumption does not overtly alter the percent of splenic DC, but does increase the surface density of CD11c on these cells. Data show that cocultures containing purified CD4+ T DO11.10 cells and APC derived from alcohol-consuming mice show decreased IL-6, IL-12, IL-17A, and IFN-gamma and increased IL-13 cytokine production in response to OVA stimulation.


CONCLUSIONS
Ethanol alters CD11c+CD8(alpha)+ DC function, affecting cytokines responsible for adaptive immune responses. A unifying hypothesis for the underlying mechanism(s) of ethanol's effect upon adaptive immune function is proposed.
Heinz
Richard
R
Northwestern University, Feinberg School of Medicine, Department of Microbiology-Immunology, Chicago, Illinois 60611, USA.
Waltenbaugh
Carl
C
D000428:Alcohol Drinking / Q000276:immunology* / Q000473:pathology; D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D040881:CD11a Antigen / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000378:metabolism
D040881:CD11a Antigen; D016827:CD8 Antigens; D002492:Central Nervous System Depressants; D018793:Interleukin-13; D020381:Interleukin-17; D015850:Interleukin-6; D018664:Interleukin-12; D000431:Ethanol; D007371:Interferon-gamma