Listeria toxin promotes phosphorylation of the inflammasome adaptor ASC through Lyn and Syk to exacerbate pathogen expansion

Tanishita, Yuko; Sekiya, Hisateru; Inohara, Naohiro; Tsuchiya, Kazuo; Mitsuyama, Masao; Núñez, Gabriel; Hara, Hideki

doi:10.1016/j.celrep.2022.110414

Cited by 8 publications

(11 citation statements)

References 73 publications

(86 reference statements)

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“…Activation of the inflammasome induced by Listeria monocytogenes infection exacerbates the host's pathological condition. 72,80,81 This response is facilitated by Listeria virulence factors such as LLO. 80,111 Similar phenomena have been reported with other pathogens, such as Staphylococcus aureus, Bacillus cereus, Streptococcus pneumoniae, Mycobacterium tuberculosis, and COVID-19.…”

Section: Discussionmentioning

confidence: 99%

“…A recent study identified threonine at amino acid 223 of LLO as a responsible amino acid in inflammasome activation. 80 A Listeria mutant harboring replacement of threonine with alanine at the position (T223A) fails to induce IL-1β production and caspase-1 activation, even though the mutant could escape into the cytosol and multiply in infected macrophages. These data indicate that LLO is essential in allowing the bacterium to escape from the phagosome and in promoting inflammasome activation independent of its pore-forming activity.…”

Section: Listeriolysin Omentioning

confidence: 99%

“…Notably, LLO contributes to the pathogenicity of Listeria monocytogenes by promoting inflammasome-mediated IL-18 production. 80,81 Thus, LLO is essential for bacterial escape and activation of inflammasome responses as an important virulence factor in macrophages and in mice infected with Listeria monocytogenes.…”

Section: Listeriolysin Omentioning

confidence: 99%

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Activation of inflammasomes and mechanisms for intracellular recognition of Listeria monocytogenes

Matsuda

Yamauchi

Hara

2023

Microbiology and Immunology

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The high mortality rate associated with Listeria monocytogenes can be attributed to its ability to invade the body systemically and to activate inflammasomes. Both of these processes are facilitated by expressing a major virulence factor known as listeriolysin O, a 56 kDa pore‐forming protein encoded by the hly gene. Listeriolysin O plays a crucial role in the pathogenesis of the bacterium by facilitating the escape of the pathogen from the phagosome into the cytosol. This process is essential for the successful establishment of infection. In addition, listeriolysin O is known as an immunomodulator that activates host signal transduction. In addition to listeriolysin O, Listeria expresses a variety of bacterial ligands, such as lipoteichoic acid, nucleotide, and flagellin, that are recognized by host intracellular pattern‐recognition receptors including Nod‐like receptors, AIM2‐like receptors, and RIG‐I‐like receptors. This review introduces intracellular recognition of Listeria monocytogenes since recent studies have revealed that the activation of inflammasome exacerbates Gram‐positive bacteria infection.

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Section: Discussionmentioning

confidence: 99%

Section: Listeriolysin Omentioning

confidence: 99%

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Activation of inflammasomes and mechanisms for intracellular recognition of Listeria monocytogenes

Matsuda

Yamauchi

Hara

2023

Microbiology and Immunology

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“…Upregulation of ASC phosphorylation was verified in a secondary step, showing that ASC phosphorylation can utilize another signaling pathway in addition to LLO-mediated Lyn-Syk kinases. These data demonstrated that pathogens could activate different inflammasomes in order to control immune responses and benefit the spread of the pathogen in the host ( 75 ).…”

Section: Gram-positive Bacteria Trigger Inflammasome Activationmentioning

confidence: 99%

Inflammasome activation by Gram-positive bacteria: Mechanisms of activation and regulation

Keestra-Gounder

Nagao

2023

Front. Immunol.

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The inflammasomes are intracellular multimeric protein complexes consisting of an innate immune sensor, the adapter protein ASC and the inflammatory caspases-1 and/or -11 and are important for the host defense against pathogens. Activaton of the receptor leads to formation of the inflammasomes and subsequent processing and activation of caspase-1 that cleaves the proinflammatory cytokines IL-1β and IL-18. Active caspase-1, and in some instances caspase-11, cleaves gasdermin D that translocates to the cell membrane where it forms pores resulting in the cell death program called pyroptosis. Inflammasomes can detect a range of microbial ligands through direct interaction or indirectly through diverse cellular processes including changes in ion fluxes, production of reactive oxygen species and disruption of various host cell functions. In this review, we will focus on the NLRP3, NLRP6, NLRC4 and AIM2 inflammasomes and how they are activated and regulated during infections with Gram-positive bacteria, including Staphylococcus spp., Streptococcus spp. and Listeria monocytogenes.

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“…Aside from pore formation the early stages of pore assembly, including receptor binding and oligomerization, have been implicated in CDC mediated host responses. For example, recent work showed that LLO binding to cholesterol‐rich membrane rafts activated inflammasomes via the Lyn‐Syk signaling cascade, 66 while binding and oligomerization of SLO, PFO, and ILY enhance membrane repair by vesicle shedding 67 . The molecular mechanisms governing CDC‐induced host cell responses in a pore‐independent manner are not well characterized.…”

Section: More Than Just Poresmentioning

confidence: 99%

Cholesterol‐dependent cytolysins: The outstanding questions

et al. 2022

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The cholesterol-dependent cytolysins (CDCs) are a major family of bacterial pore-forming proteins secreted as virulence factors by Gram-positive bacterial species. CDCs are produced as soluble, monomeric proteins that bind specifically to cholesterol-rich membranes, where they oligomerize into ring-shaped pores of more than 30 monomers. Understanding the details of the steps the toxin undergoes in converting from monomer to a membrane-spanning pore is a continuing challenge. In this review we summarize what we know about CDCs and highlight the remaining outstanding questions that require answers to obtain a complete picture of how these toxins kill cells. K E Y W O R D S CD59, cholesterol-binding protein, cholesterol-dependent cytolysin, intermedilysin, MACPF, membrane-protein interactions, perfringolysin O, pneumolysin, pore-forming toxin 1 | INTRODUCTION Pore-forming toxins (PFTs), bacterial toxins that act via membrane permeabilization, are typically produced to aid bacterial virulence or survival. Cholesterol-dependent cytolysins (CDCs) are a large family of PFTs observed in numerous Gram-positive bacterial genera including Streptococcus, Clostridium, Listeria, and Gardnerella.

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Listeria toxin promotes phosphorylation of the inflammasome adaptor ASC through Lyn and Syk to exacerbate pathogen expansion

Cited by 8 publications

References 73 publications

Activation of inflammasomes and mechanisms for intracellular recognition of Listeria monocytogenes

Activation of inflammasomes and mechanisms for intracellular recognition of Listeria monocytogenes

Inflammasome activation by Gram-positive bacteria: Mechanisms of activation and regulation

Cholesterol‐dependent cytolysins: The outstanding questions

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