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...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2017-03-01
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| Series: | mBio |
| Online Access: | https://journals.asm.org/doi/10.1128/mBio.02179-16 |
| _version_ | 1818893282907783168 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-19T18:10:08Z |
| format | Article |
| id | doaj.art-ea924052c82e4bb88cc80fbff048963b |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-12-19T18:10:08Z |
| publishDate | 2017-03-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-ea924052c82e4bb88cc80fbff048963b2022-12-21T20:11:20ZengAmerican Society for MicrobiologymBio2150-75112017-03-018110.1128/mBio.02179-16Promyelocytic Leukemia Protein (PML) Controls <italic toggle="yes">Listeria monocytogenes</italic> InfectionDavid Ribet0Valérie Lallemand-Breitenbach1Omar Ferhi2Marie-Anne Nahori3Hugo Varet4Hugues de Thé5Pascale Cossart6Institut Pasteur, Unité des Interactions Bactéries-Cellules, Paris, FranceInserm, CNRS, Université Paris Diderot, Institut Universitaire Hématologie, U944/UMR7212, Hôpital St. Louis, Paris, FranceInserm, CNRS, Université Paris Diderot, Institut Universitaire Hématologie, U944/UMR7212, Hôpital St. Louis, Paris, FranceInstitut Pasteur, Unité des Interactions Bactéries-Cellules, Paris, FranceInstitut Pasteur, Plate-forme Transcriptome et Epigenome, Biomics, Centre d’Innovation et Recherche Technologique (Citech), Paris, FranceInserm, CNRS, Université Paris Diderot, Institut Universitaire Hématologie, U944/UMR7212, Hôpital St. Louis, Paris, FranceInstitut Pasteur, Unité des Interactions Bactéries-Cellules, Paris, FranceABSTRACT 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.https://journals.asm.org/doi/10.1128/mBio.02179-16 |
| spellingShingle | 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 mBio |
| title | 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_short | 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 |
| url | https://journals.asm.org/doi/10.1128/mBio.02179-16 |
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