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Skin Immunization Obviates Alcohol-Related Immune Dysfunction
Alcoholics suffer from immune dysfunction that can impede vaccine efficacy. If ethanol (EtOH)-induced immune impairment is in part a result of direct exposure of immune cells to EtOH, then reduced levels of exposure could result in less immune dysfunction. As alcohol ingestion results in lower alcoh...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4693267/ https://www.ncbi.nlm.nih.gov/pubmed/26561838 http://dx.doi.org/10.3390/biom5043009 |
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author | Brand, Rhonda M. Stottlemyer, John Mark Cline, Rachel A. Donahue, Cara Behari, Jaideep Falo, Louis D. |
author_facet | Brand, Rhonda M. Stottlemyer, John Mark Cline, Rachel A. Donahue, Cara Behari, Jaideep Falo, Louis D. |
author_sort | Brand, Rhonda M. |
collection | PubMed |
description | Alcoholics suffer from immune dysfunction that can impede vaccine efficacy. If ethanol (EtOH)-induced immune impairment is in part a result of direct exposure of immune cells to EtOH, then reduced levels of exposure could result in less immune dysfunction. As alcohol ingestion results in lower alcohol levels in skin than blood, we hypothesized that the skin immune network may be relatively preserved, enabling skin-targeted immunizations to obviate the immune inhibitory effects of alcohol consumption on conventional vaccines. We employed the two most common chronic EtOH mouse feeding models, the liver-damaging Lieber-DeCarli (LD) and liver-sparing Meadows-Cook (MC) diets, to examine the roles of EtOH and/or EtOH-induced liver dysfunction on alcohol related immunosuppression. Pair-fed mice were immunized against the model antigen ovalbumin (OVA) by DNA immunization or against flu by administering the protein-based influenza vaccine either systemically (IV, IM), directly to liver (hydrodynamic), or cutaneously (biolistic, ID). We measured resulting tissue EtOH levels, liver stress, regulatory T cell (Treg), and myeloid-derived suppressor cell (MDSC) populations. We compared immune responsiveness by measuring delayed-type hypersensitivity (DTH), antigen-specific cytotoxic T lymphocyte (CTL), and antibody induction as a function of delivery route and feeding model. We found that, as expected, and independent of the feeding model, EtOH ingestion inhibits DTH, CTL lysis, and antigen-specific total IgG induced by traditional systemic vaccines. On the other hand, skin-targeted vaccines were equally immunogenic in alcohol-exposed and non-exposed subjects, suggesting that cutaneous immunization may result in more efficacious vaccination in alcohol-ingesting subjects. |
format | Online Article Text |
id | pubmed-4693267 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-46932672016-01-07 Skin Immunization Obviates Alcohol-Related Immune Dysfunction Brand, Rhonda M. Stottlemyer, John Mark Cline, Rachel A. Donahue, Cara Behari, Jaideep Falo, Louis D. Biomolecules Article Alcoholics suffer from immune dysfunction that can impede vaccine efficacy. If ethanol (EtOH)-induced immune impairment is in part a result of direct exposure of immune cells to EtOH, then reduced levels of exposure could result in less immune dysfunction. As alcohol ingestion results in lower alcohol levels in skin than blood, we hypothesized that the skin immune network may be relatively preserved, enabling skin-targeted immunizations to obviate the immune inhibitory effects of alcohol consumption on conventional vaccines. We employed the two most common chronic EtOH mouse feeding models, the liver-damaging Lieber-DeCarli (LD) and liver-sparing Meadows-Cook (MC) diets, to examine the roles of EtOH and/or EtOH-induced liver dysfunction on alcohol related immunosuppression. Pair-fed mice were immunized against the model antigen ovalbumin (OVA) by DNA immunization or against flu by administering the protein-based influenza vaccine either systemically (IV, IM), directly to liver (hydrodynamic), or cutaneously (biolistic, ID). We measured resulting tissue EtOH levels, liver stress, regulatory T cell (Treg), and myeloid-derived suppressor cell (MDSC) populations. We compared immune responsiveness by measuring delayed-type hypersensitivity (DTH), antigen-specific cytotoxic T lymphocyte (CTL), and antibody induction as a function of delivery route and feeding model. We found that, as expected, and independent of the feeding model, EtOH ingestion inhibits DTH, CTL lysis, and antigen-specific total IgG induced by traditional systemic vaccines. On the other hand, skin-targeted vaccines were equally immunogenic in alcohol-exposed and non-exposed subjects, suggesting that cutaneous immunization may result in more efficacious vaccination in alcohol-ingesting subjects. MDPI 2015-11-06 /pmc/articles/PMC4693267/ /pubmed/26561838 http://dx.doi.org/10.3390/biom5043009 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Brand, Rhonda M. Stottlemyer, John Mark Cline, Rachel A. Donahue, Cara Behari, Jaideep Falo, Louis D. Skin Immunization Obviates Alcohol-Related Immune Dysfunction |
title | Skin Immunization Obviates Alcohol-Related Immune Dysfunction |
title_full | Skin Immunization Obviates Alcohol-Related Immune Dysfunction |
title_fullStr | Skin Immunization Obviates Alcohol-Related Immune Dysfunction |
title_full_unstemmed | Skin Immunization Obviates Alcohol-Related Immune Dysfunction |
title_short | Skin Immunization Obviates Alcohol-Related Immune Dysfunction |
title_sort | skin immunization obviates alcohol-related immune dysfunction |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4693267/ https://www.ncbi.nlm.nih.gov/pubmed/26561838 http://dx.doi.org/10.3390/biom5043009 |
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