Mimicking the intestinal host–pathogen interactions in a 3D In vitro model: The role of the mucus layer

The intestinal mucus lines the luminal surface of the intestinal epithelium. This mucus is a dynamic semipermeable barrier and one of the first-line defense mechanisms against the outside environment, protecting the body against chemical, mechanical, or biological external insults. At the same time,...

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Autores: García-Díaz, Maria, Cendra Gascón, María del Mar|||0000-0002-2100-2406, Alonso Roman, Raquel, Urdániz, María, Torrents Serra, Eduard, Martínez, Elena
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Universitat Politècnica de Catalunya (UPC)
Repositorio:UPCommons. Portal del coneixement obert de la UPC
Idioma:inglés
OAI Identifier:oai:upcommons.upc.edu:2117/380978
Acceso en línea:https://hdl.handle.net/2117/380978
https://dx.doi.org/10.3390/pharmaceutics14081552
Access Level:acceso abierto
Palabra clave:Intestinal mucosa
3D in vitro models
Intestinal models
Host–pathogen interaction
Intestinal mucus
Hydrogels
Mucosa intestinal
Àrees temàtiques de la UPC::Ciències de la salut::Medicina::Farmacologia
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spelling Mimicking the intestinal host–pathogen interactions in a 3D In vitro model: The role of the mucus layerGarcía-Díaz, MariaCendra Gascón, María del Mar|||0000-0002-2100-2406Alonso Roman, RaquelUrdániz, MaríaTorrents Serra, EduardMartínez, ElenaIntestinal mucosa3D in vitro modelsIntestinal modelsHost–pathogen interactionIntestinal mucusHydrogelsMucosa intestinalÀrees temàtiques de la UPC::Ciències de la salut::Medicina::FarmacologiaThe intestinal mucus lines the luminal surface of the intestinal epithelium. This mucus is a dynamic semipermeable barrier and one of the first-line defense mechanisms against the outside environment, protecting the body against chemical, mechanical, or biological external insults. At the same time, the intestinal mucus accommodates the resident microbiota, providing nutrients and attachment sites, and therefore playing an essential role in the host–pathogen interactions and gut homeostasis. Underneath this mucus layer, the intestinal epithelium is organized into finger-like protrusions called villi and invaginations called crypts. This characteristic 3D architecture is known to influence the epithelial cell differentiation and function. However, when modelling in vitro the intestinal host–pathogen interactions, these two essential features, the intestinal mucus and the 3D topography are often not represented, thus limiting the relevance of the models. Here we present an in vitro model that mimics the small intestinal mucosa and its interactions with intestinal pathogens in a relevant manner, containing the secreted mucus layer and the epithelial barrier in a 3D villus-like hydrogel scaffold. This 3D architecture significantly enhanced the secretion of mucus. In infection with the pathogenic adherent invasive E. coli strain LF82, characteristic of Crohn’s disease, we observed that this secreted mucus promoted the adhesion of the pathogen and at the same time had a protective effect upon its invasion. This pathogenic strain was able to survive inside the epithelial cells and trigger an inflammatory response that was milder when a thick mucus layer was present. Thus, we demonstrated that our model faithfully mimics the key features of the intestinal mucosa necessary to study the interactions with intestinal pathogens.Multidisciplinary Digital Publishing Institute (MDPI)20222022-07-2620232023-01-24journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/2117/380978https://dx.doi.org/10.3390/pharmaceutics14081552reponame:UPCommons. Portal del coneixement obert de la UPCinstname:Universitat Politècnica de Catalunya (UPC)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:upcommons.upc.edu:2117/3809782026-05-27T15:37:01Z
dc.title.none.fl_str_mv Mimicking the intestinal host–pathogen interactions in a 3D In vitro model: The role of the mucus layer
title Mimicking the intestinal host–pathogen interactions in a 3D In vitro model: The role of the mucus layer
spellingShingle Mimicking the intestinal host–pathogen interactions in a 3D In vitro model: The role of the mucus layer
García-Díaz, Maria
Intestinal mucosa
3D in vitro models
Intestinal models
Host–pathogen interaction
Intestinal mucus
Hydrogels
Mucosa intestinal
Àrees temàtiques de la UPC::Ciències de la salut::Medicina::Farmacologia
title_short Mimicking the intestinal host–pathogen interactions in a 3D In vitro model: The role of the mucus layer
title_full Mimicking the intestinal host–pathogen interactions in a 3D In vitro model: The role of the mucus layer
title_fullStr Mimicking the intestinal host–pathogen interactions in a 3D In vitro model: The role of the mucus layer
title_full_unstemmed Mimicking the intestinal host–pathogen interactions in a 3D In vitro model: The role of the mucus layer
title_sort Mimicking the intestinal host–pathogen interactions in a 3D In vitro model: The role of the mucus layer
dc.creator.none.fl_str_mv García-Díaz, Maria
Cendra Gascón, María del Mar|||0000-0002-2100-2406
Alonso Roman, Raquel
Urdániz, María
Torrents Serra, Eduard
Martínez, Elena
author García-Díaz, Maria
author_facet García-Díaz, Maria
Cendra Gascón, María del Mar|||0000-0002-2100-2406
Alonso Roman, Raquel
Urdániz, María
Torrents Serra, Eduard
Martínez, Elena
author_role author
author2 Cendra Gascón, María del Mar|||0000-0002-2100-2406
Alonso Roman, Raquel
Urdániz, María
Torrents Serra, Eduard
Martínez, Elena
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Intestinal mucosa
3D in vitro models
Intestinal models
Host–pathogen interaction
Intestinal mucus
Hydrogels
Mucosa intestinal
Àrees temàtiques de la UPC::Ciències de la salut::Medicina::Farmacologia
topic Intestinal mucosa
3D in vitro models
Intestinal models
Host–pathogen interaction
Intestinal mucus
Hydrogels
Mucosa intestinal
Àrees temàtiques de la UPC::Ciències de la salut::Medicina::Farmacologia
description The intestinal mucus lines the luminal surface of the intestinal epithelium. This mucus is a dynamic semipermeable barrier and one of the first-line defense mechanisms against the outside environment, protecting the body against chemical, mechanical, or biological external insults. At the same time, the intestinal mucus accommodates the resident microbiota, providing nutrients and attachment sites, and therefore playing an essential role in the host–pathogen interactions and gut homeostasis. Underneath this mucus layer, the intestinal epithelium is organized into finger-like protrusions called villi and invaginations called crypts. This characteristic 3D architecture is known to influence the epithelial cell differentiation and function. However, when modelling in vitro the intestinal host–pathogen interactions, these two essential features, the intestinal mucus and the 3D topography are often not represented, thus limiting the relevance of the models. Here we present an in vitro model that mimics the small intestinal mucosa and its interactions with intestinal pathogens in a relevant manner, containing the secreted mucus layer and the epithelial barrier in a 3D villus-like hydrogel scaffold. This 3D architecture significantly enhanced the secretion of mucus. In infection with the pathogenic adherent invasive E. coli strain LF82, characteristic of Crohn’s disease, we observed that this secreted mucus promoted the adhesion of the pathogen and at the same time had a protective effect upon its invasion. This pathogenic strain was able to survive inside the epithelial cells and trigger an inflammatory response that was milder when a thick mucus layer was present. Thus, we demonstrated that our model faithfully mimics the key features of the intestinal mucosa necessary to study the interactions with intestinal pathogens.
publishDate 2022
dc.date.none.fl_str_mv 2022
2022-07-26
2023
2023-01-24
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/2117/380978
https://dx.doi.org/10.3390/pharmaceutics14081552
url https://hdl.handle.net/2117/380978
https://dx.doi.org/10.3390/pharmaceutics14081552
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute (MDPI)
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute (MDPI)
dc.source.none.fl_str_mv reponame:UPCommons. Portal del coneixement obert de la UPC
instname:Universitat Politècnica de Catalunya (UPC)
instname_str Universitat Politècnica de Catalunya (UPC)
reponame_str UPCommons. Portal del coneixement obert de la UPC
collection UPCommons. Portal del coneixement obert de la UPC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.301603

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