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A mouse model of binge alcohol consumption and Burkholderia infection
BACKGROUND: Binge drinking, an increasingly common form of alcohol consumption, is associated with increased mortality and morbidity; yet, its effects on the immune system’s ability to defend against infectious agents are poorly understood. Burkholderia pseudomallei, the causative agent of melioidos...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6261616/ https://www.ncbi.nlm.nih.gov/pubmed/30485380 http://dx.doi.org/10.1371/journal.pone.0208061 |
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author | Jimenez, Victor Moreno, Ryan Settles, Erik Currie, Bart J. Keim, Paul Monroy, Fernando P. |
author_facet | Jimenez, Victor Moreno, Ryan Settles, Erik Currie, Bart J. Keim, Paul Monroy, Fernando P. |
author_sort | Jimenez, Victor |
collection | PubMed |
description | BACKGROUND: Binge drinking, an increasingly common form of alcohol consumption, is associated with increased mortality and morbidity; yet, its effects on the immune system’s ability to defend against infectious agents are poorly understood. Burkholderia pseudomallei, the causative agent of melioidosis can occur in healthy humans, yet binge alcohol use is progressively being recognized as a major risk factor. Although our previous studies demonstrated that binge alcohol exposure results in reduced alveolar macrophage function and increased Burkholderia virulence in vitro, no experimental studies have investigated the outcomes of binge alcohol on Burkholderia spp. infection in vivo. PRINCIPAL FINDINGS: In this study, we used the close genetic relatives of B. pseudomallei, B. thailandensis E264 and B. vietnamiensis, as useful BSL-2 model systems. Eight-week-old female C57BL/6 mice were administered alcohol comparable to human binge drinking episodes (4.4 g/kg) or PBS intraperitoneally 30 min before a non-lethal intranasal infection. In an initial B. thailandensis infection (3 x 10(5)), bacteria accumulated in the lungs and disseminated to the spleen in alcohol administered mice only, compared with PBS treated mice at 24 h PI. The greatest bacterial load occurred with B. vietnamiensis (1 x 10(6)) in lungs, spleen, and brain tissue by 72 h PI. Pulmonary cytokine expression (TNF-α, GM-CSF) decreased, while splenic cytokine (IL-10) increased in binge drunk mice. Increased lung and brain permeability was observed as early as 2 h post alcohol administration in vivo. Trans-epithelial electrical resistance (TEER) was significantly decreased, while intracellular invasion of non-phagocytic cells increased with 0.2% v/v alcohol exposure in vitro. CONCLUSIONS: Our results indicate that a single binge alcohol dose suppressed innate immune functions and increased the ability of less virulent Burkholderia strains to disseminate through increased barrier permeability and intracellular invasion of non-phagocytic cells. |
format | Online Article Text |
id | pubmed-6261616 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-62616162018-12-19 A mouse model of binge alcohol consumption and Burkholderia infection Jimenez, Victor Moreno, Ryan Settles, Erik Currie, Bart J. Keim, Paul Monroy, Fernando P. PLoS One Research Article BACKGROUND: Binge drinking, an increasingly common form of alcohol consumption, is associated with increased mortality and morbidity; yet, its effects on the immune system’s ability to defend against infectious agents are poorly understood. Burkholderia pseudomallei, the causative agent of melioidosis can occur in healthy humans, yet binge alcohol use is progressively being recognized as a major risk factor. Although our previous studies demonstrated that binge alcohol exposure results in reduced alveolar macrophage function and increased Burkholderia virulence in vitro, no experimental studies have investigated the outcomes of binge alcohol on Burkholderia spp. infection in vivo. PRINCIPAL FINDINGS: In this study, we used the close genetic relatives of B. pseudomallei, B. thailandensis E264 and B. vietnamiensis, as useful BSL-2 model systems. Eight-week-old female C57BL/6 mice were administered alcohol comparable to human binge drinking episodes (4.4 g/kg) or PBS intraperitoneally 30 min before a non-lethal intranasal infection. In an initial B. thailandensis infection (3 x 10(5)), bacteria accumulated in the lungs and disseminated to the spleen in alcohol administered mice only, compared with PBS treated mice at 24 h PI. The greatest bacterial load occurred with B. vietnamiensis (1 x 10(6)) in lungs, spleen, and brain tissue by 72 h PI. Pulmonary cytokine expression (TNF-α, GM-CSF) decreased, while splenic cytokine (IL-10) increased in binge drunk mice. Increased lung and brain permeability was observed as early as 2 h post alcohol administration in vivo. Trans-epithelial electrical resistance (TEER) was significantly decreased, while intracellular invasion of non-phagocytic cells increased with 0.2% v/v alcohol exposure in vitro. CONCLUSIONS: Our results indicate that a single binge alcohol dose suppressed innate immune functions and increased the ability of less virulent Burkholderia strains to disseminate through increased barrier permeability and intracellular invasion of non-phagocytic cells. Public Library of Science 2018-11-28 /pmc/articles/PMC6261616/ /pubmed/30485380 http://dx.doi.org/10.1371/journal.pone.0208061 Text en © 2018 Jimenez et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Jimenez, Victor Moreno, Ryan Settles, Erik Currie, Bart J. Keim, Paul Monroy, Fernando P. A mouse model of binge alcohol consumption and Burkholderia infection |
title | A mouse model of binge alcohol consumption and Burkholderia infection |
title_full | A mouse model of binge alcohol consumption and Burkholderia infection |
title_fullStr | A mouse model of binge alcohol consumption and Burkholderia infection |
title_full_unstemmed | A mouse model of binge alcohol consumption and Burkholderia infection |
title_short | A mouse model of binge alcohol consumption and Burkholderia infection |
title_sort | mouse model of binge alcohol consumption and burkholderia infection |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6261616/ https://www.ncbi.nlm.nih.gov/pubmed/30485380 http://dx.doi.org/10.1371/journal.pone.0208061 |
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