A Role for PML in Innate Immunity

Lunardi, Andrea; Gáboli, Mirella; Giorgio, Marco; Rivi, Roberta; Bygrave, Anne E.; Antoniou, Michael; Drabek, Dubravka; Dzierzak, Elaine; Fagioli, Marta; Salmena, Leonardo; Botto, Marina; Cordon‐Cardo, Carlos; Luzzatto, Lucio; Pelicci, Pier Giuseppe; Grosveld, Frank; Pandolfi, Pier Paolo

doi:10.1177/1947601911402682

Cited by 43 publications

(44 citation statements)

References 44 publications

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“…30 The attenuated IL-1b production in Pml 2/2 macrophages was not caused by impaired expression of NLRP3 inflammasome components. The expression of NLRP3, ASC, and procaspase-1 was normal in bone marrow-derived macrophages ( Figure 1B).…”

Section: Resultsmentioning

confidence: 95%

Selective inhibition of the NLRP3 inflammasome by targeting to promyelocytic leukemia protein in mouse and human

Huang

et al. 2013

Blood

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Section: Resultsmentioning

confidence: 95%

Selective inhibition of the NLRP3 inflammasome by targeting to promyelocytic leukemia protein in mouse and human

Huang

et al. 2013

Blood

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Section: Pml and Innate Immune Signalingmentioning

confidence: 98%

“…For instance, the production of the proinflammatory cytokines interleukin 1␤ (IL-1␤) and IL-6 has been reported to be markedly decreased in PML-deficient cells (34,35). In accordance with a deregulation of IL-6 that has a prominent role in the acute-phase response, PML knockout mice display an aberrant immune response to bacterial infections and are resistant to acute lipopolysaccharide (LPS)-mediated lethality (34). These data encourage the hypothesis that the coregulatory role of PML in innate immune signaling may be even broader than anticipated from previous studies and may include thus-far-unrecognized biological functions, such as the regulation of acute inflammatory responses during viral infections.…”

Section: Pml and Innate Immune Signalingmentioning

confidence: 99%

Emerging Role of PML Nuclear Bodies in Innate Immune Signaling

Scherer

Stamminger

2016

J Virol

150

168

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Research in the last 2 decades has demonstrated that a specific organelle of the cell nucleus, termed PML nuclear body (PML-NB) or nuclear domain 10 (ND10), is frequently modified during viral infection. This correlates with antagonization of a direct repressive function of individual PML-NB components, such as the PML, hDaxx, Sp100, or ATRX protein, that are able to act as cellular restriction factors. Recent studies now reveal an emerging role of PML-NBs as coregulatory structures of both type I and type II interferon responses. This emphasizes that targeting of PML-NBs by viral regulatory proteins has evolved as a strategy to compromise intrinsic antiviral defense and innate immune responses. P romyelocytic leukemia (PML) protein, a member of the tripartite motif (TRIM) protein family, is the key component of subnuclear structures known as PML nuclear bodies (PML-NBs) or nuclear domains 10 (ND10). PML-NBs are dynamic foci that consist of numerous permanently or transiently associated proteins and, consequently, have been implicated in the regulation of diverse cellular functions, including the cell cycle, apoptosis, senescence, stress, and DNA damage responses (reviewed in reference 1). Although the underlying biochemical function of these subnuclear structures is still unclear, three models can be found in the literature, proposing PML-NBs to be nuclear protein depots, sites of nuclear activities (e.g., transcription), or hotspots for posttranslational modifications. In particular, since nearly all PMLassociated proteins are modified by SUMO and SUMOylation of PML is essential for the integrity of PML-NBs, these structures may form "catalytic surfaces" for SUMOylation (1). This is of importance since recent studies suggest that the SUMO pathway is required for the regulation of innate immune signaling and intrinsic immunity during viral infection (reviewed in reference 2). The observation that PML-NBs are targeted and modified by many viruses during infection set off a longstanding debate as to whether PML-NBs exert a pro-or antiviral function and led to a fruitful area of virology research over the past 20 years. Interestingly, these studies revealed that viruses, even representatives of the same virus family, trigger diverse modifications of PML-NBs during infection, ranging from proteasomal degradation of NB components by herpes simplex virus type 1 (HSV-1), to dispersal of PML-NBs by human cytomegalovirus (HCMV), to a rearrangement of PML-NB foci into nuclear track-like structures by adenoviruses or a relocalization of PML into cytoplasmic bodies by HIV-1 (3-5). While there are a few examples of viral factors that undergo interactions with PML-NBs in order to exploit these structures for the benefit of the virus, the main body of evidence supports a role of PML-NBs as components of the antiviral defense against a variety of DNA and RNA viruses (reviewed in reference 3). PML-NBs AND INTRINSIC IMMUNITYThe role of PML-NBs in intrinsic immunity, which represents the first line of intracellular defense agains...

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“…In contrast to PML’s established action against viruses, a single study mentioned that PML knockout mice are more sensitive to infection by Listeria monocytogenes (37). However, the exact role of PML in anti- Listeria responses or in other bacterial infections has not been elucidated.…”

Section: Introductionmentioning

confidence: 99%

Promyelocytic Leukemia Protein (PML) ControlsListeria monocytogenesInfection

Ribet

Lallemand-Breitenbach

Ferhi

et al. 2017

mBio

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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.

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A Role for PML in Innate Immunity

Cited by 43 publications

References 44 publications

Selective inhibition of the NLRP3 inflammasome by targeting to promyelocytic leukemia protein in mouse and human

Selective inhibition of the NLRP3 inflammasome by targeting to promyelocytic leukemia protein in mouse and human

Emerging Role of PML Nuclear Bodies in Innate Immune Signaling

Promyelocytic Leukemia Protein (PML) ControlsListeria monocytogenesInfection

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