Chronic ethanol exposure affects in vivo migration of hepatic dendritic cells to secondary lymphoid tissue

Lau, Audrey H.; Thomson, Angus W.; Colvin, Bridget L.

doi:10.1016/j.humimm.2007.03.008

Cited by 18 publications

(19 citation statements)

References 51 publications

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“…By contrast, splenic alcohol-exposed DC had reduced capacity to prime naïve T cells compared to control splenic DC that corresponded with in vitro phenotypic maturation and functional data [81]. However, the Review Trends in Immunology Vol.…”

Section: Macrophages: Impact On Chemokine Productionmentioning

confidence: 58%

“…30 No.1 enhanced priming ability of alcohol-exposed hepatic DC did not correspond with and, in fact, conflicted with phenotypic and in vitro functional data. Examination of DC migration to draining lymph nodes in vivo revealed enhanced migration of alcohol-exposed hepatic DC [81]. The altered migration of hepatic alcohol-exposed DC was found to be independent of both CC chemokine receptor 7 and CD11a expression.…”

Section: Macrophages: Impact On Chemokine Productionmentioning

confidence: 90%

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Antigen-presenting cells under the influence of alcohol

Lau¹,

Szabó²,

Thomson³

2009

Trends in Immunology

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Section: Macrophages: Impact On Chemokine Productionmentioning

confidence: 58%

Section: Macrophages: Impact On Chemokine Productionmentioning

confidence: 90%

Antigen-presenting cells under the influence of alcohol

Lau¹,

Szabó²,

Thomson³

2009

Trends in Immunology

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“…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).…”

Section: Discussionmentioning

confidence: 99%

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

Hemann

McGill

Legge

2014

Alcoholism Clin & Exp Res

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Background It is well established that chronic ethanol (EtOH) consumption is associated with increased incidence and disease severity of respiratory infections. Our recent work demonstrates this increase in disease severity to influenza virus (IAV) infections is due, in part, to a failure to mount a robust IAV-specific CD8 T cell response along with a specific impairment in the ability of these T cells to produce IFNγ. However, the full extent of the lesion in the effector CD8 T cell compartment during chronic EtOH consumption remains unknown. Methods Utilizing the Meadows-Cook murine model of chronic alcohol consumption, mice received EtOH in their drinking water for 8 or 12 weeks. Mice were challenged intranasally with IAV and the activation and effector functions of IAV specific CD8 T cells were determined in both the lung-draining lymph nodes and lungs. Results Our results confirm the defect in interferon γ (IFNγ) production, however, the ability of IAV-specific T cells to produce tumor necrosis factor α (TNFα) and interleukin-2 (IL-2) in EtOH-consuming mice remains unaltered while interferon γ (IFNγ) production. In contrast, EtOH consumption significantly reduces the ability of CD8 T cells to degranulate and kill IAV-specific targets. Finally, our findings suggest the lesion begins during the initial activation of CD8 T cells, as we observe early defects in proliferation in the lung-draining lymph nodes (dLN) of IAV-infected, EtOH-consuming mice. Conclusions These findings highlight the previously unrecognized depth of the lesion in the IAV-specific CD8 T cell response during chronic EtOH consumption. Given the important role CD8 T cell immunity plays in control of IAV, these findings may aid in the development of vaccination and/or therapeutic strategies to reverse these defects in the CD8 T cell response and reduce serious disease outcomes associated with IAV infections in alcoholics.

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“…Chronic alcoholics have increased susceptibility to and severity of infection (reviewed in Cook, 1998; MacGregor and Louria, 1997; Szabo, 1999), and evidence is strong that this is because of impaired innate and adaptive immunity. Dendritic cells (DC) play a key role in the initiation of adaptive immune responses, and various aspects of DC function are negatively impacted by acute and chronic ethanol (EtOH) exposure in humans (Dolganiuc et al, 2003; Laso et al, 2007; Mandrekar et al, 2004) and mice (Aloman et al, 2007; Heinz and Waltenbaugh, 2007; Lau et al, 2006, 2007; Ness et al, 2008). In addition to dysfunction of individual DC, alterations in DC numbers could contribute to impaired immune responses because of lack of sufficient antigen presentation interactions to stimulate a robust T cell response or because of increased induction of regulatory T cells (Treg).…”

mentioning

confidence: 99%

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

Edsen-Moore

Fan

Ness

et al. 2008

Alcoholism Clin & Exp Res

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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.

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Chronic ethanol exposure affects in vivo migration of hepatic dendritic cells to secondary lymphoid tissue

Cited by 18 publications

References 51 publications

Antigen-presenting cells under the influence of alcohol

Antigen-presenting cells under the influence of alcohol

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

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

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