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PI3-kinase activation is critical for host barrier permissiveness to Listeria monocytogenes

Invasion of nonphagocytic cells, a critical property of Listeria monocytogenes (Lm) that enables it to cross host barriers, is mediated by the interaction of two bacterial surface proteins, InlA and InlB, with their respective receptors E-cadherin and c-Met. Although InlA–E-cadherin interaction is n...

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Autores principales: Gessain, Grégoire, Tsai, Yu-Huan, Travier, Laetitia, Bonazzi, Matteo, Grayo, Solène, Cossart, Pascale, Charlier, Caroline, Disson, Olivier, Lecuit, Marc
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4322052/
https://www.ncbi.nlm.nih.gov/pubmed/25624443
http://dx.doi.org/10.1084/jem.20141406
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author Gessain, Grégoire
Tsai, Yu-Huan
Travier, Laetitia
Bonazzi, Matteo
Grayo, Solène
Cossart, Pascale
Charlier, Caroline
Disson, Olivier
Lecuit, Marc
author_facet Gessain, Grégoire
Tsai, Yu-Huan
Travier, Laetitia
Bonazzi, Matteo
Grayo, Solène
Cossart, Pascale
Charlier, Caroline
Disson, Olivier
Lecuit, Marc
author_sort Gessain, Grégoire
collection PubMed
description Invasion of nonphagocytic cells, a critical property of Listeria monocytogenes (Lm) that enables it to cross host barriers, is mediated by the interaction of two bacterial surface proteins, InlA and InlB, with their respective receptors E-cadherin and c-Met. Although InlA–E-cadherin interaction is necessary and sufficient for Lm crossing of the intestinal barrier, both InlA and InlB are required for Lm crossing of the placental barrier. The mechanisms underlying these differences are unknown. Phosphoinositide 3-kinase (PI3-K) is involved in both InlA- and InlB-dependent pathways. Indeed, InlA-dependent entry requires PI3-K activity but does not activate it, whereas InlB–c-Met interaction activates PI3-K. We show that Lm intestinal target cells exhibit a constitutive PI3-K activity, rendering InlB dispensable for InlA-dependent Lm intestinal barrier crossing. In contrast, the placental barrier does not exhibit constitutive PI3-K activity, making InlB necessary for InlA-dependent Lm placental invasion. Here, we provide the molecular explanation for the respective contributions of InlA and InlB to Lm host barrier invasion, and reveal the critical role of InlB in rendering cells permissive to InlA-mediated invasion. This study shows that PI3-K activity is critical to host barrier permissiveness to microbes, and that pathogens exploit both similarities and differences of host barriers to disseminate.
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spelling pubmed-43220522015-08-09 PI3-kinase activation is critical for host barrier permissiveness to Listeria monocytogenes Gessain, Grégoire Tsai, Yu-Huan Travier, Laetitia Bonazzi, Matteo Grayo, Solène Cossart, Pascale Charlier, Caroline Disson, Olivier Lecuit, Marc J Exp Med Article Invasion of nonphagocytic cells, a critical property of Listeria monocytogenes (Lm) that enables it to cross host barriers, is mediated by the interaction of two bacterial surface proteins, InlA and InlB, with their respective receptors E-cadherin and c-Met. Although InlA–E-cadherin interaction is necessary and sufficient for Lm crossing of the intestinal barrier, both InlA and InlB are required for Lm crossing of the placental barrier. The mechanisms underlying these differences are unknown. Phosphoinositide 3-kinase (PI3-K) is involved in both InlA- and InlB-dependent pathways. Indeed, InlA-dependent entry requires PI3-K activity but does not activate it, whereas InlB–c-Met interaction activates PI3-K. We show that Lm intestinal target cells exhibit a constitutive PI3-K activity, rendering InlB dispensable for InlA-dependent Lm intestinal barrier crossing. In contrast, the placental barrier does not exhibit constitutive PI3-K activity, making InlB necessary for InlA-dependent Lm placental invasion. Here, we provide the molecular explanation for the respective contributions of InlA and InlB to Lm host barrier invasion, and reveal the critical role of InlB in rendering cells permissive to InlA-mediated invasion. This study shows that PI3-K activity is critical to host barrier permissiveness to microbes, and that pathogens exploit both similarities and differences of host barriers to disseminate. The Rockefeller University Press 2015-02-09 /pmc/articles/PMC4322052/ /pubmed/25624443 http://dx.doi.org/10.1084/jem.20141406 Text en © 2015 Gessain et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Article
Gessain, Grégoire
Tsai, Yu-Huan
Travier, Laetitia
Bonazzi, Matteo
Grayo, Solène
Cossart, Pascale
Charlier, Caroline
Disson, Olivier
Lecuit, Marc
PI3-kinase activation is critical for host barrier permissiveness to Listeria monocytogenes
title PI3-kinase activation is critical for host barrier permissiveness to Listeria monocytogenes
title_full PI3-kinase activation is critical for host barrier permissiveness to Listeria monocytogenes
title_fullStr PI3-kinase activation is critical for host barrier permissiveness to Listeria monocytogenes
title_full_unstemmed PI3-kinase activation is critical for host barrier permissiveness to Listeria monocytogenes
title_short PI3-kinase activation is critical for host barrier permissiveness to Listeria monocytogenes
title_sort pi3-kinase activation is critical for host barrier permissiveness to listeria monocytogenes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4322052/
https://www.ncbi.nlm.nih.gov/pubmed/25624443
http://dx.doi.org/10.1084/jem.20141406
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