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Microbially competent 3D skin: a test system that reveals insight into host–microbe interactions and their potential toxicological impact

The skin`s microbiome is predominantly commensalic, harbouring a metabolic potential far exceeding that of its host. While there is clear evidence that bacteria-dependent metabolism of pollutants modulates the toxicity for the host there is still a lack of models for investigating causality of micro...

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Autores principales: Lemoine, Lisa, Dieckmann, Ralf, Al Dahouk, Sascha, Vincze, Szilvia, Luch, Andreas, Tralau, Tewes
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502063/
https://www.ncbi.nlm.nih.gov/pubmed/32681188
http://dx.doi.org/10.1007/s00204-020-02841-z
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author Lemoine, Lisa
Dieckmann, Ralf
Al Dahouk, Sascha
Vincze, Szilvia
Luch, Andreas
Tralau, Tewes
author_facet Lemoine, Lisa
Dieckmann, Ralf
Al Dahouk, Sascha
Vincze, Szilvia
Luch, Andreas
Tralau, Tewes
author_sort Lemoine, Lisa
collection PubMed
description The skin`s microbiome is predominantly commensalic, harbouring a metabolic potential far exceeding that of its host. While there is clear evidence that bacteria-dependent metabolism of pollutants modulates the toxicity for the host there is still a lack of models for investigating causality of microbiome-associated pathophysiology or toxicity. We now report on a biologically characterised microbial–skin tissue co-culture that allows studying microbe–host interactions for extended periods of time in situ. The system is based on a commercially available 3D skin model. In a proof-of-concept, this model was colonised with single and mixed cultures of two selected skin commensals. Two different methods were used to quantify the bacteria on the surface of the skin models. While Micrococcus luteus established a stable microbial–skin tissue co-culture, Pseudomonas oleovorans maintained slow continuous growth over the 8-day cultivation period. A detailed skin transcriptome analysis showed bacterial colonisation leading to up to 3318 significant changes. Additionally, FACS, ELISA and Western blot analyses were carried out to analyse secretion of cytokines and growth factors. Changes found in colonised skin varied depending on the bacterial species used and comprised immunomodulatory functions, such as secretion of IL-1α/β, Il-6, antimicrobial peptides and increased gene transcription of IL-10 and TLR2. The colonisation also influenced the secretion of growth factors such as VFGFA and FGF2. Notably, many of these changes have already previously been associated with the presence of skin commensals. Concomitantly, the model gained first insights on the microbiome’s influence on skin xenobiotic metabolism (i.e., CYP1A1, CYP1B1 and CYP2D6) and olfactory receptor expression. The system provides urgently needed experimental access for assessing the toxicological impact of microbiome-associated xenobiotic metabolism in situ. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00204-020-02841-z) contains supplementary material, which is available to authorized users.
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spelling pubmed-75020632020-10-01 Microbially competent 3D skin: a test system that reveals insight into host–microbe interactions and their potential toxicological impact Lemoine, Lisa Dieckmann, Ralf Al Dahouk, Sascha Vincze, Szilvia Luch, Andreas Tralau, Tewes Arch Toxicol In Vitro Systems The skin`s microbiome is predominantly commensalic, harbouring a metabolic potential far exceeding that of its host. While there is clear evidence that bacteria-dependent metabolism of pollutants modulates the toxicity for the host there is still a lack of models for investigating causality of microbiome-associated pathophysiology or toxicity. We now report on a biologically characterised microbial–skin tissue co-culture that allows studying microbe–host interactions for extended periods of time in situ. The system is based on a commercially available 3D skin model. In a proof-of-concept, this model was colonised with single and mixed cultures of two selected skin commensals. Two different methods were used to quantify the bacteria on the surface of the skin models. While Micrococcus luteus established a stable microbial–skin tissue co-culture, Pseudomonas oleovorans maintained slow continuous growth over the 8-day cultivation period. A detailed skin transcriptome analysis showed bacterial colonisation leading to up to 3318 significant changes. Additionally, FACS, ELISA and Western blot analyses were carried out to analyse secretion of cytokines and growth factors. Changes found in colonised skin varied depending on the bacterial species used and comprised immunomodulatory functions, such as secretion of IL-1α/β, Il-6, antimicrobial peptides and increased gene transcription of IL-10 and TLR2. The colonisation also influenced the secretion of growth factors such as VFGFA and FGF2. Notably, many of these changes have already previously been associated with the presence of skin commensals. Concomitantly, the model gained first insights on the microbiome’s influence on skin xenobiotic metabolism (i.e., CYP1A1, CYP1B1 and CYP2D6) and olfactory receptor expression. The system provides urgently needed experimental access for assessing the toxicological impact of microbiome-associated xenobiotic metabolism in situ. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00204-020-02841-z) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2020-07-17 2020 /pmc/articles/PMC7502063/ /pubmed/32681188 http://dx.doi.org/10.1007/s00204-020-02841-z Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle In Vitro Systems
Lemoine, Lisa
Dieckmann, Ralf
Al Dahouk, Sascha
Vincze, Szilvia
Luch, Andreas
Tralau, Tewes
Microbially competent 3D skin: a test system that reveals insight into host–microbe interactions and their potential toxicological impact
title Microbially competent 3D skin: a test system that reveals insight into host–microbe interactions and their potential toxicological impact
title_full Microbially competent 3D skin: a test system that reveals insight into host–microbe interactions and their potential toxicological impact
title_fullStr Microbially competent 3D skin: a test system that reveals insight into host–microbe interactions and their potential toxicological impact
title_full_unstemmed Microbially competent 3D skin: a test system that reveals insight into host–microbe interactions and their potential toxicological impact
title_short Microbially competent 3D skin: a test system that reveals insight into host–microbe interactions and their potential toxicological impact
title_sort microbially competent 3d skin: a test system that reveals insight into host–microbe interactions and their potential toxicological impact
topic In Vitro Systems
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502063/
https://www.ncbi.nlm.nih.gov/pubmed/32681188
http://dx.doi.org/10.1007/s00204-020-02841-z
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