Effects of Chronic Ethanol Feeding on Murine Dendritic Cell Numbers, Turnover Rate, and Dendropoiesis

Abstract

Background Chronic alcoholics have increased susceptibility to and severity of infection, which are likely to be a result of impaired immune defense mechanisms. The contribution of dendritic cells (DC) to these immune defense changes is not well understood. Alterations in DC numbers, dendropoiesis, and lifespan have not been specifically studied in vivo in chronic ethanol (EtOH) exposure models. As DC play an essential role in initiating immune responses, alterations in these DC characteristics would help explain changes observed in adaptive immune responses. Methods Mice received 20% EtOH (w/v) in the drinking water for up to 28 weeks, with mouse chow ad libitum. In EtOH-fed and water control mice, DC were enumerated by flow cytometry. The effect of EtOH on DC precursor numbers was determined by differentiation in vitro in the presence of granulocyte-macrophage colony-stimulating factor and interleukin-4, and the effect of an EtOH environment on untreated DC differentiation was measured following bone marrow transfer to irradiated hosts. DC turnover rate was also examined by bromodeoxyuridine incorporation and loss. Results The percentage and absolute numbers of DC were decreased in spleen and increased in thymus beginning as early as 4 weeks of EtOH feeding. In addition, the overall cellularity of spleen and thymus were altered by this regimen. However, chronic EtOH consumption did not adversely affect DC precursor numbers, differentiation abilities, or turnover rates. Conclusions Decreased splenic DC numbers observed following chronic murine EtOH consumption are not because of altered DC precursor numbers or differentiation, nor increased DC turnover rate. Similarly, increased thymic DC numbers are not the result of alterations in DC precursor differentiation or turnover rate. Compartment size plays a role in determining splenic and thymic DC numbers following chronic EtOH feeding. EtOH-induced alterations in total DC numbers provide several mechanisms to partially explain why chronic alcoholics have increased susceptibility to infections.

A Recent Perspective on Alcohol, Immunity, and Host Defense

“…This model has recently been proposed as mimicking human chronic alcohol use without liver disease (Cook et al, 2007). Consistent with this, there is lack of features of alcoholic liver disease but there are manifestations of immune alterations including innate and adaptive immune cell defects developing after various length of time of alcohol treatment (Cook et al, 2007; Edsen-Moore et al, 2008). …”

Antigen-presenting cells under the influence of alcohol

“…Reduced numbers of DC in the spleen, but increased numbers in the thymus, are seen in mice given 20% ethanol in drinking water for up to 28 weeks [79]. These changes could not be ascribed to altered DC precursor numbers, differentiation or turnover rate.…”

Chronic Ethanol Exposure Selectively Inhibits the Influenza‐Specific CD8 T Cell Response During Influenza A Virus Infection

“…However, it is likely that other defects within mice chronically consuming EtOH (such as IL-2 expression by CD4 T cells and defects within APCs) contribute to inappropriate and/or insufficient priming of IAV-specific CD8 T cells within dLN. Changes in antigen presenting cell populations have been well documented to occur during EtOH exposure (Fan et al, 2011, Ness et al, 2008, Parlet and Schlueter, 2013, Edsen-Moore et al, 2008, Legge and Waldschmidt, 2014, Gurung et al, 2009, Buttari et al, 2008, Happel and Nelson, 2005, Joshi and Guidot, 2007, Szabo and Mandrekar, 2009, Zhang et al, 2002, Eken et al, 2011, Joshi et al, 2005, Lau et al, 2007, Mehta and Guidot, 2012, Rendon et al, 2012, Siggins et al, 2009, Szabo and Mandrekar, 2008). While dendritic cell functionality during IAV challenge of mice chronically consuming EtOH has not been completely investigated, the migration of dermal DCs, cutaneous DCs and Langerhans cells is delayed following FITC sensitization (Ness et al, 2008, Parlet and Schlueter, 2013).…”