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Yersinia Pseudotuberculosis Modulates Regulatory T Cell Stability via Injection of Yersinia Outer Proteins in a Type III Secretion System-Dependent Manner

Adaptive immunity is essentially required to control acute infection with enteropathogenic Yersinia pseudotuberculosis (Yptb). We have recently demonstrated that Yptb can directly modulate naïve CD4(+) T cell differentiation. However, whether fully differentiated forkhead box protein P3 (Foxp3(+)) r...

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Autores principales: Elfiky, Ahmed, Bonifacius, Agnes, Pezoldt, Joern, Pasztoi, Maria, Chaoprasid, Paweena, Sadana, Pooja, El-Sherbeeny, Nagla, Hagras, Magda, Scrima, Andrea, Dersch, Petra, Huehn, Jochen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Akadémiai Kiadó 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6348704/
https://www.ncbi.nlm.nih.gov/pubmed/30719325
http://dx.doi.org/10.1556/1886.2018.00015
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author Elfiky, Ahmed
Bonifacius, Agnes
Pezoldt, Joern
Pasztoi, Maria
Chaoprasid, Paweena
Sadana, Pooja
El-Sherbeeny, Nagla
Hagras, Magda
Scrima, Andrea
Dersch, Petra
Huehn, Jochen
author_facet Elfiky, Ahmed
Bonifacius, Agnes
Pezoldt, Joern
Pasztoi, Maria
Chaoprasid, Paweena
Sadana, Pooja
El-Sherbeeny, Nagla
Hagras, Magda
Scrima, Andrea
Dersch, Petra
Huehn, Jochen
author_sort Elfiky, Ahmed
collection PubMed
description Adaptive immunity is essentially required to control acute infection with enteropathogenic Yersinia pseudotuberculosis (Yptb). We have recently demonstrated that Yptb can directly modulate naïve CD4(+) T cell differentiation. However, whether fully differentiated forkhead box protein P3 (Foxp3(+)) regulatory T cells (Tregs), fundamental key players to maintain immune homeostasis, are targeted by Yptb remains elusive. Here, we demonstrate that within the CD4(+) T cell compartment Yptb preferentially targets Tregs and injects Yersinia outer proteins (Yops) in a process that depends on the type III secretion system and invasins. Remarkably, Yop-translocation into ex vivo isolated Foxp3(+) Tregs resulted in a substantial downregulation of Foxp3 expression and a decreased capacity to express the immunosuppressive cytokine interleukin-10 (IL-10). Together, these findings highlight that invasins are critically required to mediate Yptb attachment to Foxp3(+) Tregs, which allows efficient Yop-translocation and finally enables the modulation of the Foxp3(+) Tregs' suppressive phenotype.
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spelling pubmed-63487042019-02-04 Yersinia Pseudotuberculosis Modulates Regulatory T Cell Stability via Injection of Yersinia Outer Proteins in a Type III Secretion System-Dependent Manner Elfiky, Ahmed Bonifacius, Agnes Pezoldt, Joern Pasztoi, Maria Chaoprasid, Paweena Sadana, Pooja El-Sherbeeny, Nagla Hagras, Magda Scrima, Andrea Dersch, Petra Huehn, Jochen Eur J Microbiol Immunol (Bp) Original Research Paper Adaptive immunity is essentially required to control acute infection with enteropathogenic Yersinia pseudotuberculosis (Yptb). We have recently demonstrated that Yptb can directly modulate naïve CD4(+) T cell differentiation. However, whether fully differentiated forkhead box protein P3 (Foxp3(+)) regulatory T cells (Tregs), fundamental key players to maintain immune homeostasis, are targeted by Yptb remains elusive. Here, we demonstrate that within the CD4(+) T cell compartment Yptb preferentially targets Tregs and injects Yersinia outer proteins (Yops) in a process that depends on the type III secretion system and invasins. Remarkably, Yop-translocation into ex vivo isolated Foxp3(+) Tregs resulted in a substantial downregulation of Foxp3 expression and a decreased capacity to express the immunosuppressive cytokine interleukin-10 (IL-10). Together, these findings highlight that invasins are critically required to mediate Yptb attachment to Foxp3(+) Tregs, which allows efficient Yop-translocation and finally enables the modulation of the Foxp3(+) Tregs' suppressive phenotype. Akadémiai Kiadó 2018-11-28 /pmc/articles/PMC6348704/ /pubmed/30719325 http://dx.doi.org/10.1556/1886.2018.00015 Text en © 2018, The Author(s) http://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted use, distribution, and reproduction in any medium for non-commercial purposes, provided the original author and source are credited, a link to the CC License is provided, and changes - if any - are indicated.
spellingShingle Original Research Paper
Elfiky, Ahmed
Bonifacius, Agnes
Pezoldt, Joern
Pasztoi, Maria
Chaoprasid, Paweena
Sadana, Pooja
El-Sherbeeny, Nagla
Hagras, Magda
Scrima, Andrea
Dersch, Petra
Huehn, Jochen
Yersinia Pseudotuberculosis Modulates Regulatory T Cell Stability via Injection of Yersinia Outer Proteins in a Type III Secretion System-Dependent Manner
title Yersinia Pseudotuberculosis Modulates Regulatory T Cell Stability via Injection of Yersinia Outer Proteins in a Type III Secretion System-Dependent Manner
title_full Yersinia Pseudotuberculosis Modulates Regulatory T Cell Stability via Injection of Yersinia Outer Proteins in a Type III Secretion System-Dependent Manner
title_fullStr Yersinia Pseudotuberculosis Modulates Regulatory T Cell Stability via Injection of Yersinia Outer Proteins in a Type III Secretion System-Dependent Manner
title_full_unstemmed Yersinia Pseudotuberculosis Modulates Regulatory T Cell Stability via Injection of Yersinia Outer Proteins in a Type III Secretion System-Dependent Manner
title_short Yersinia Pseudotuberculosis Modulates Regulatory T Cell Stability via Injection of Yersinia Outer Proteins in a Type III Secretion System-Dependent Manner
title_sort yersinia pseudotuberculosis modulates regulatory t cell stability via injection of yersinia outer proteins in a type iii secretion system-dependent manner
topic Original Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6348704/
https://www.ncbi.nlm.nih.gov/pubmed/30719325
http://dx.doi.org/10.1556/1886.2018.00015
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