Listeria monocytogenes and the Inflammasome: From Cytosolic Bacteriolysis to Tumor Immunotherapy

Theisen, Erin; Sauer, John-Demian

doi:10.1007/978-3-319-41171-2_7

Cited by 23 publications

(17 citation statements)

References 112 publications

(215 reference statements)

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“…The large number of inflammasome complexes activated upon F . novicida infection is reminiscent of what have been observed during infection with other intracellular bacteria [ 11 , 53 , 54 ], although F . novicida infection of murine macrophages is somewhat unique due to its high dependence on AIM2 [ 18 ].…”

Section: Discussionmentioning

confidence: 92%

IFN-γ extends the immune functions of Guanylate Binding Proteins to inflammasome-independent antibacterial activities during Francisella novicida infection

Wallet¹,

Benaoudia²,

Mosnier³

et al. 2017

PLoS Pathog

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Guanylate binding proteins (GBPs) are interferon-inducible proteins involved in the cell-intrinsic immunity against numerous intracellular pathogens. The molecular mechanisms underlying the potent antibacterial activity of GBPs are still unclear. GBPs have been functionally linked to the NLRP3, the AIM2 and the caspase-11 inflammasomes. Two opposing models are currently proposed to explain the GBPs-inflammasome link: i) GBPs would target intracellular bacteria or bacteria-containing vacuoles to increase cytosolic PAMPs release ii) GBPs would directly facilitate inflammasome complex assembly. Using Francisella novicida infection, we investigated the functional interactions between GBPs and the inflammasome. GBPs, induced in a type I IFN-dependent manner, are required for the F. novicida-mediated AIM2-inflammasome pathway. Here, we demonstrate that GBPs action is not restricted to the AIM2 inflammasome, but controls in a hierarchical manner the activation of different inflammasomes complexes and apoptotic caspases. IFN-γ induces a quantitative switch in GBPs levels and redirects pyroptotic and apoptotic pathways under the control of GBPs. Furthermore, upon IFN-γ priming, F. novicida-infected macrophages restrict cytosolic bacterial replication in a GBP-dependent and inflammasome-independent manner. Finally, in a mouse model of tularemia, we demonstrate that the inflammasome and the GBPs are two key immune pathways functioning largely independently to control F. novicida infection. Altogether, our results indicate that GBPs are the master effectors of IFN-γ-mediated responses against F. novicida to control antibacterial immune responses in inflammasome-dependent and independent manners.

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Section: Discussionmentioning

confidence: 92%

IFN-γ extends the immune functions of Guanylate Binding Proteins to inflammasome-independent antibacterial activities during Francisella novicida infection

Wallet¹,

Benaoudia²,

Mosnier³

et al. 2017

PLoS Pathog

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“…It is thought that L. monocytogenes maintains a low-level of inflammasome activation in order to establish a successful infection. Hence, an L. monocytogenes strain engineered to activate the NLRC4 inflammasome was substantially attenuated in the murine model of infection [57,58]. …”

Section: Pathogens Differentially Interfere With the Inflammasomes Anmentioning

confidence: 99%

Checks and Balances between Autophagy and Inflammasomes during Infection

Seveau

Turner

Gavrilin

et al. 2018

Journal of Molecular Biology

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Autophagy and inflammasome complex assembly are physiological processes that control homeostasis, inflammation, and immunity. Autophagy is a ubiquitous pathway that degrades cytosolic macromolecules or organelles, as well as intracellular pathogens. Inflammasomes are multi-protein complexes that assemble in the cytosol of cells upon detection of pathogen- or danger-associated molecular patterns. A critical outcome of inflammasome assembly is the activation of the serine protease caspase-1, which activates the pro-inflammatory cytokine precursors pro-IL-1β and pro-IL-18. Studies on chronic inflammatory diseases, heart diseases, Alzheimer's disease, and multiple sclerosis revealed that autophagy and inflammasomes intersect and regulate each other. In the context of infectious diseases, however, less is known about the interplay between autophagy and inflammasome assembly, although it is becoming evident that pathogens have evolved multiple strategies to inhibit and/or subvert these pathways and to take advantage of their intricate crosstalk. An improved appreciation of these pathways and their subversion by diverse pathogens is expected to help in the design of anti-infective therapeutic interventions.

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“…The intracellular pathogen Listeria monocytogenes secretes a toxin, listeriolysin (LLO), which activates the NLRP3 inflammasome via K + efflux. 52,53 LLO also induces DRP1-and OPA1independent fission by modulating the membranes shared between the ER and mitochondria (MAMs), 54 hinting at a novel ERdependent fission mechanism. MAMs are emerging as important signalling hubs between the ER and mitochondria and are a possible site of NLRP3 inflammasome assembly.…”

Section: Bacterial Infectionmentioning

confidence: 99%

The rOX‐stars of inflammation: links between the inflammasome and mitochondrial meltdown

Holley

Schroder

2020

Clin & Trans Imm

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The nod-like receptor protein 3 (NLRP3) inflammasome drives inflammation in response to mitochondrial dysfunction. As metabolic powerhouses with prokaryotic ancestry, mitochondria are a cache for danger-associated molecular patterns and pathogen-associated molecular pattern-like molecules that elicit potent innate immune responses. Persistent mitochondrial damage caused by infection, or genetic or environmental factors, can lead to inappropriate or sustained inflammasome signalling. Here, we review the features of mitochondria that drive inflammatory signalling, with a particular focus on mitochondrial activation of the NLRP3 inflammasome. Given that mitochondrial network dynamics, metabolic activity and redox state are all intricately linked to each other and to NLRP3 inflammasome activity, we highlight the importance of a holistic approach to investigations of NLRP3 activation by dysfunctional mitochondria.

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Listeria monocytogenes and the Inflammasome: From Cytosolic Bacteriolysis to Tumor Immunotherapy

Cited by 23 publications

References 112 publications

IFN-γ extends the immune functions of Guanylate Binding Proteins to inflammasome-independent antibacterial activities during Francisella novicida infection

IFN-γ extends the immune functions of Guanylate Binding Proteins to inflammasome-independent antibacterial activities during Francisella novicida infection

Checks and Balances between Autophagy and Inflammasomes during Infection

The rOX‐stars of inflammation: links between the inflammasome and mitochondrial meltdown

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