Promyelocytic Leukemia Protein (PML) Controls <italic toggle="yes">Listeria monocytogenes</italic> Infection

ABSTRACT The promyelocytic leukemia protein (PML) is the main organizer of stress-responsive subnuclear structures called PML nuclear bodies. These structures recruit multiple interactors and modulate their abundance or their posttranslational modifications, notably by the SUMO ubiquitin-like modifi...

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Autores principales:	David Ribet, Valérie Lallemand-Breitenbach, Omar Ferhi, Marie-Anne Nahori, Hugo Varet, Hugues de Thé, Pascale Cossart
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/ea924052c82e4bb88cc80fbff048963b
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spelling	oai:doaj.org-article:ea924052c82e4bb88cc80fbff048963b2021-11-15T15:51:06ZPromyelocytic Leukemia Protein (PML) Controls <italic toggle="yes">Listeria monocytogenes</italic> Infection10.1128/mBio.02179-162150-7511https://doaj.org/article/ea924052c82e4bb88cc80fbff048963b2017-03-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02179-16https://doaj.org/toc/2150-7511ABSTRACT The promyelocytic leukemia protein (PML) is the main organizer of stress-responsive subnuclear structures called PML nuclear bodies. These structures recruit multiple interactors and modulate their abundance or their posttranslational modifications, notably by the SUMO ubiquitin-like modifiers. The involvement of PML in antiviral responses is well established. In contrast, the role of PML in bacterial infection remains poorly characterized. Here, we show that PML restricts infection by the pathogenic bacterium Listeria monocytogenes but not by Salmonella enterica serovar Typhimurium. During infection, PML undergoes oxidation-mediated multimerization, associates with the nuclear matrix, and becomes de-SUMOylated due to the pore-forming activity of the Listeria toxin listeriolysin O (LLO). These events trigger an antibacterial response that is not observed during in vitro infection by an LLO-defective Listeria mutant, but which can be phenocopied by specific induction of PML de-SUMOylation. Using transcriptomic and proteomic microarrays, we also characterized a network of immunity genes and cytokines, which are regulated by PML in response to Listeria infection but independently from the listeriolysin O toxin. Our study thus highlights two mechanistically distinct complementary roles of PML in host responses against bacterial infection. IMPORTANCE The promyelocytic leukemia protein (PML) is a eukaryotic protein that can polymerize in discrete nuclear assemblies known as PML nuclear bodies (NBs) and plays essential roles in many different cellular processes. Key to its function, PML can be posttranslationally modified by SUMO, a ubiquitin-like modifier. Identification of the role of PML in antiviral defenses has been deeply documented. In contrast, the role of PML in antibacterial defenses remains elusive. Here, we identify two mechanistically distinct complementary roles of PML in antibacterial responses against pathogens such as Listeria: (i) we show that PML regulates the expression of immunity genes in response to bacterial infection, and (ii) we unveil the fact that modification of PML SUMOylation by bacterial pore-forming toxins is sensed as a danger signal, leading to a restriction of bacterial intracellular multiplication. Taken together, our data reinforce the concept that intranuclear bodies can dynamically regulate important processes, such as defense against invaders.David RibetValérie Lallemand-BreitenbachOmar FerhiMarie-Anne NahoriHugo VaretHugues de ThéPascale CossartAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 8, Iss 1 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 David Ribet Valérie Lallemand-Breitenbach Omar Ferhi Marie-Anne Nahori Hugo Varet Hugues de Thé Pascale Cossart Promyelocytic Leukemia Protein (PML) Controls <italic toggle="yes">Listeria monocytogenes</italic> Infection
description	ABSTRACT The promyelocytic leukemia protein (PML) is the main organizer of stress-responsive subnuclear structures called PML nuclear bodies. These structures recruit multiple interactors and modulate their abundance or their posttranslational modifications, notably by the SUMO ubiquitin-like modifiers. The involvement of PML in antiviral responses is well established. In contrast, the role of PML in bacterial infection remains poorly characterized. Here, we show that PML restricts infection by the pathogenic bacterium Listeria monocytogenes but not by Salmonella enterica serovar Typhimurium. During infection, PML undergoes oxidation-mediated multimerization, associates with the nuclear matrix, and becomes de-SUMOylated due to the pore-forming activity of the Listeria toxin listeriolysin O (LLO). These events trigger an antibacterial response that is not observed during in vitro infection by an LLO-defective Listeria mutant, but which can be phenocopied by specific induction of PML de-SUMOylation. Using transcriptomic and proteomic microarrays, we also characterized a network of immunity genes and cytokines, which are regulated by PML in response to Listeria infection but independently from the listeriolysin O toxin. Our study thus highlights two mechanistically distinct complementary roles of PML in host responses against bacterial infection. IMPORTANCE The promyelocytic leukemia protein (PML) is a eukaryotic protein that can polymerize in discrete nuclear assemblies known as PML nuclear bodies (NBs) and plays essential roles in many different cellular processes. Key to its function, PML can be posttranslationally modified by SUMO, a ubiquitin-like modifier. Identification of the role of PML in antiviral defenses has been deeply documented. In contrast, the role of PML in antibacterial defenses remains elusive. Here, we identify two mechanistically distinct complementary roles of PML in antibacterial responses against pathogens such as Listeria: (i) we show that PML regulates the expression of immunity genes in response to bacterial infection, and (ii) we unveil the fact that modification of PML SUMOylation by bacterial pore-forming toxins is sensed as a danger signal, leading to a restriction of bacterial intracellular multiplication. Taken together, our data reinforce the concept that intranuclear bodies can dynamically regulate important processes, such as defense against invaders.
format	article
author	David Ribet Valérie Lallemand-Breitenbach Omar Ferhi Marie-Anne Nahori Hugo Varet Hugues de Thé Pascale Cossart
author_facet	David Ribet Valérie Lallemand-Breitenbach Omar Ferhi Marie-Anne Nahori Hugo Varet Hugues de Thé Pascale Cossart
author_sort	David Ribet
title	Promyelocytic Leukemia Protein (PML) Controls <italic toggle="yes">Listeria monocytogenes</italic> Infection
title_short	Promyelocytic Leukemia Protein (PML) Controls <italic toggle="yes">Listeria monocytogenes</italic> Infection
title_full	Promyelocytic Leukemia Protein (PML) Controls <italic toggle="yes">Listeria monocytogenes</italic> Infection
title_fullStr	Promyelocytic Leukemia Protein (PML) Controls <italic toggle="yes">Listeria monocytogenes</italic> Infection
title_full_unstemmed	Promyelocytic Leukemia Protein (PML) Controls <italic toggle="yes">Listeria monocytogenes</italic> Infection
title_sort	promyelocytic leukemia protein (pml) controls <italic toggle="yes">listeria monocytogenes</italic> infection
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/ea924052c82e4bb88cc80fbff048963b
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Promyelocytic Leukemia Protein (PML) Controls <italic toggle="yes">Listeria monocytogenes</italic> Infection

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