BACKGROUND: Chronic alcoholics experience increased incidence and severity of infections, the mechanism of which is incompletely understood. Dendritic cells (DC) migrate from peripheral locations to lymph nodes (LN) to initiate adaptive immunity against infection. Little is known about how chronic alcohol exposure affects skin DC numbers or migration. METHODS: Mice received 20% EtOH in the drinking water for up to 35 weeks. Baseline Langerhans cell (LC) and dermal DC (dDC) numbers were enumerated by immunofluorescence (IF). LC repopulation after inflammation was determined following congenic bone marrow (BM) transplant and ultraviolet (UV) irradiation. Net LC loss from epidermis was determined by IF following TNF-alpha or CpG stimulation. LC and dDC migration into LN was assessed by flow cytometry following epicutaneous FITC administration. RESULTS: Chronic EtOH consumption caused a baseline reduction in LC but not dDC numbers. The deficit was not corrected following transplantation with non-EtOH-exposed BM and UV irradiation, supporting the hypothesis that the defect is intrinsic to the skin environment rather than LC precursors. Net loss of LC from epidermis following inflammation was greatly reduced in EtOH-fed mice versus controls. Ethanol consumption for at least 4 weeks led to delayed LC migration into LN, and consumption for at least 8 weeks led to delayed dDC migration into LN following epicutaneous FITC application. CONCLUSIONS: Chronic EtOH consumption causes decreased density of epidermal LC, which likely results in decreased epidermal immunosurveillance. It also results in altered migratory responsiveness and delayed LC and dDC migration into LN, which likely delays activation of adaptive immunity. Decreased LC density at baseline appears to be the result of an alteration in the skin environment rather than an intrinsic LC defect. These findings provide novel mechanisms to at least partially explain why chronic alcoholics are more susceptible to infections, especially those following skin penetration.
BACKGROUND: Chronic alcoholics experience increased incidence and severity of infections, the mechanism of which is incompletely understood. Dendritic cells (DC) migrate from peripheral locations to lymph nodes (LN) to initiate adaptive immunity against infection. Little is known about how chronic alcohol exposure affects skin DC numbers or migration. METHODS:Mice received 20% EtOH in the drinking water for up to 35 weeks. Baseline Langerhans cell (LC) and dermal DC (dDC) numbers were enumerated by immunofluorescence (IF). LC repopulation after inflammation was determined following congenic bone marrow (BM) transplant and ultraviolet (UV) irradiation. Net LC loss from epidermis was determined by IF following TNF-alpha or CpG stimulation. LC and dDC migration into LN was assessed by flow cytometry following epicutaneous FITC administration. RESULTS: Chronic EtOH consumption caused a baseline reduction in LC but not dDC numbers. The deficit was not corrected following transplantation with non-EtOH-exposed BM and UV irradiation, supporting the hypothesis that the defect is intrinsic to the skin environment rather than LC precursors. Net loss of LC from epidermis following inflammation was greatly reduced in EtOH-fed mice versus controls. Ethanol consumption for at least 4 weeks led to delayed LC migration into LN, and consumption for at least 8 weeks led to delayed dDC migration into LN following epicutaneous FITC application. CONCLUSIONS: Chronic EtOH consumption causes decreased density of epidermal LC, which likely results in decreased epidermal immunosurveillance. It also results in altered migratory responsiveness and delayed LC and dDC migration into LN, which likely delays activation of adaptive immunity. Decreased LC density at baseline appears to be the result of an alteration in the skin environment rather than an intrinsic LC defect. These findings provide novel mechanisms to at least partially explain why chronic alcoholics are more susceptible to infections, especially those following skin penetration.
Authors: D N Cook; D M Prosser; R Forster; J Zhang; N A Kuklin; S J Abbondanzo; X D Niu; S C Chen; D J Manfra; M T Wiekowski; L M Sullivan; S R Smith; H B Greenberg; S K Narula; M Lipp; S A Lira Journal: Immunity Date: 2000-05 Impact factor: 31.745
Authors: Miriam Merad; Markus G Manz; Holger Karsunky; Amy Wagers; Wendy Peters; Israel Charo; Irving L Weissman; Jason G Cyster; Edgar G Engleman Journal: Nat Immunol Date: 2002-11-04 Impact factor: 25.606
Authors: Kejing Song; Ruth A Coleman; Xiaoyan Zhu; Carol Alber; Zuhair K Ballas; Thomas J Waldschmidt; Robert T Cook Journal: J Leukoc Biol Date: 2002-12 Impact factor: 4.962
Authors: Francisco Javier Laso; José Miguel Vaquero; Julia Almeida; Miguel Marcos; Alberto Orfao Journal: Alcohol Clin Exp Res Date: 2007-03-26 Impact factor: 3.455
Authors: Ji Fan; Michelle R Edsen-Moore; Lucas E Turner; Robert T Cook; Kevin L Legge; Thomas J Waldschmidt; Annette J Schlueter Journal: Alcohol Clin Exp Res Date: 2010-10-06 Impact factor: 3.455
Authors: Prajwal Gurung; Betty M Young; Ruth A Coleman; Susan Wiechert; Lucas E Turner; Nancy B Ray; Thomas J Waldschmidt; Kevin L Legge; Robert T Cook Journal: J Leukoc Biol Date: 2008-09-26 Impact factor: 4.962
Authors: Anita Zahs; Robert T Cook; Thomas J Waldschimdt; Mashkoor A Choudhry; Elizabeth J Kovacs; Melanie D Bird Journal: Alcohol Date: 2011-09-14 Impact factor: 2.405
Authors: Nympha B D'Souza El-Guindy; Elizabeth J Kovacs; Philippe De Witte; Claudia Spies; John M Littleton; Willem J S de Villiers; Amanda J Lott; Timothy P Plackett; Nadine Lanzke; Gary G Meadows Journal: Alcohol Clin Exp Res Date: 2010-06-25 Impact factor: 3.455
Authors: David K Meyerholz; Michelle Edsen-Moore; Jodi McGill; Ruth A Coleman; Robert T Cook; Kevin L Legge Journal: J Immunol Date: 2008-07-01 Impact factor: 5.422
Authors: Michelle R Edsen-Moore; Ji Fan; Kristin J Ness; Jacquie R Marietta; Robert T Cook; Annette J Schlueter Journal: Alcohol Clin Exp Res Date: 2008-07 Impact factor: 3.455