Uptake of Tropheryma whipplei by Intestinal Epithelia

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dc.contributor.authorFriebel, Julián
dc.contributor.authorSchinnerling, Katina
dc.contributor.authorWeigt, Kathleen
dc.contributor.authorHeldt, Claudia
dc.contributor.authorFromm, Anja
dc.contributor.authorBojarski, Christian
dc.contributor.authorSiegmund, Britta
dc.contributor.authorEpple, Hans-Jörg
dc.contributor.authorKikhney, Judith
dc.contributor.authorMoter, Annette
dc.contributor.authorSchneider, Thomas
dc.contributor.authorSchulzke, Jörg D.
dc.date.accessioned2024-01-02T20:55:31Z
dc.date.available2024-01-02T20:55:31Z
dc.date.issued2023-04
dc.descriptionIndexación: Scopus.es
dc.description.abstractBackground: Tropheryma whipplei (TW) can cause different pathologies, e.g., Whipple’s disease and transient gastroenteritis. The mechanism by which the bacteria pass the intestinal epithelial barrier, and the mechanism of TW-induced gastroenteritis are currently unknown. Methods: Using ex vivo disease models comprising human duodenal mucosa exposed to TW in Ussing chambers, various intestinal epithelial cell (IEC) cultures exposed to TW and a macrophage/IEC coculture model served to characterize endocytic uptake mechanisms and barrier function. Results: TW exposed ex vivo to human small intestinal mucosae is capable of autonomously entering IECs, thereby invading the mucosa. Using dominant-negative mutants, TW uptake was shown to be dynamin- and caveolin-dependent but independent of clathrin-mediated endocytosis. Complementary inhibitor experiments suggested a role for the activation of the Ras/Rac1 pathway and actin polymerization. TW-invaded IECs underwent apoptosis, thereby causing an epithelial barrier defect, and were subsequently subject to phagocytosis by macrophages. Conclusions: TW enters epithelia via an actin-, dynamin-, caveolin-, and Ras-Rac1-dependent endocytosis mechanism and consecutively causes IEC apoptosis primarily in IECs invaded by multiple TW bacteria. This results in a barrier leak. Moreover, we propose that TW-packed IECs can be subject to phagocytic uptake by macrophages, thereby opening a potential entry point of TW into intestinal macrophages.es
dc.description.urihttps://www-scopus-com.recursosbiblioteca.unab.cl/record/display.uri?eid=2-s2.0-85152348544&origin=resultslist&sort=plf-f&src=s&nlo=&nlr=&nls=&sid=479e01fe7cbdeb24061470b900710719&sot=aff&sdt=cl&cluster=scofreetoread%2c%22all%22%2ct&sl=34&s=AF-ID%2860002636%29+AND+SUBJAREA%28CENG%29&relpos=19&citeCnt=0&searchTerm=
dc.identifier.citationInternational Journal of Molecular Sciences, Open Access, Volume 24, Issue 7April 2023 Article number 6197es
dc.identifier.doi10.3390/ijms24076197
dc.identifier.issn16616596
dc.identifier.urihttps://repositorio.unab.cl/xmlui/handle/ria/54573
dc.language.isoenes
dc.publisherMDPIes
dc.rights.licenseCC BY 4.0 DEED Attribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectApoptosises
dc.subjectBarrier functiones
dc.subjectCaveolines
dc.subjectEndocytosises
dc.subjectGastroenteritises
dc.subjectInvasiones
dc.subjectTropheryma whippleies
dc.subjectUssing chamberes
dc.subjectWhipple’s diseasees
dc.titleUptake of Tropheryma whipplei by Intestinal Epitheliaes
dc.typeArtículoes
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