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

Grégoire Gessain, Yu Huan Tsai, Laetitia Travier, Matteo Bonazzi, Solène Grayo, Pascale Cossart, Caroline Charlier, Olivier Disson, Marc Lecuit*

*此作品的通信作者

研究成果: Article同行評審

55 引文 斯高帕斯(Scopus)

摘要

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.

原文English
頁(從 - 到)165-183
頁數19
期刊Journal of Experimental Medicine
212
發行號2
DOIs
出版狀態Published - 9 2月 2015

指紋

深入研究「PI3-kinase activation is critical for host barrier permissiveness to Listeria monocytogenes」主題。共同形成了獨特的指紋。

引用此