Toll or Interleukin-1 Receptor (TIR) Domain-containing Adaptor Inducing Interferon-β (TRIF)-mediated Caspase-11 Protease Production Integrates Toll-like Receptor 4 (TLR4) Protein- and Nlrp3 Inflammasome-mediated Host Defense against Enteropathogens

Gurung, Prajwal; Malireddi, R. K. Subbarao; Anand, Paras; Demon, Dieter; Walle, Lieselotte Vande; Liu, Zhiping; Vogel, Peter; Lamkanfi, Mohamed; Kanneganti, Thirumala‐Devi

doi:10.1074/jbc.m112.401406

Cited by 222 publications

(211 citation statements)

References 40 publications

(39 reference statements)

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“…Thus, all of the noncanonical caspase-1 activation pathways described so far converge at the point of NLRP3 activation (12,13,18,19), which is consistent with NLRP3 being capable of integrating signals from different microbial agonists. We predict that, similar to the canonical caspase-1 signaling pathways, caspase-11 activation requires an upstream protein(s) capable of sensing a microbial or endogenous danger signal.…”

Section: Discussionmentioning

confidence: 50%

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Caspase-11 stimulates rapid flagellin-independent pyroptosis in response to Legionella pneumophila

Case

Kohler

Lima

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

244

265

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A flagellin-independent caspase-1 activation pathway that does not require NAIP5 or NRLC4 is induced by the intracellular pathogen Legionella pneumophila. Here we demonstrate that this pathway requires caspase-11. Treatment of macrophages with LPS up-regulated the host components required for this caspase-11 activation pathway. Activation by Legionella differed from caspase-11 activation using previously described agonists in that Legionella caspase-11 activation was rapid and required bacteria with a functional type IV secretion system called Dot/Icm. Legionella activation of caspase-11 induced pyroptosis by a mechanism independent of the NAIP/ NLRC4 and caspase-1 axis. Legionella activation of caspase-11 stimulated activation of caspase-1 through NLRP3 and ASC. Induction of caspase-11-dependent responses occurred in macrophages deficient in the adapter proteins TRIF or MyD88 but not in macrophages deficient in both signaling factors. Although caspase-11 was produced in macrophages deficient in the type-I IFN receptor, there was a severe defect in caspase-11-dependent pyroptosis in these cells. These data indicate that macrophages respond to microbial signatures to produce proteins that mediate a capsase-11 response and that the caspase-11 system provides an alternative pathway for rapid detection of an intracellular pathogen capable of evading the canonical caspase-1 activation system that responds to bacterial flagellin.innate immunity | cell death | inflammasome

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Section: Discussionmentioning

confidence: 50%

“…Casp1/11 -/- 13, 18,19). By contrast, Legionella activated the caspase-11-dependent pathway within 4 h of infection, which suggested that activation of caspase-11 could occur by different pathways depending on the bacterial agonist.…”

Section: Discussionmentioning

confidence: 91%

Caspase-11 stimulates rapid flagellin-independent pyroptosis in response to Legionella pneumophila

Case

Kohler

Lima

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

244

265

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“…LPS-stimulated bone marrow-derived macrophages (BMDMs) of caspase-11 -/-mice were defective in IL-1β secretion when exposed to cholera toxin b (CtB) or when infected with Gram-negative enteropathogens such as C. rodentium, Vibrio cholerae and E. coli (Kayagaki et al, 2011). Subsequent studies demonstrated that caspase-11 expression and activation downstream of Toll-like receptor 4-(TLR) and TIR-domain-containing adapter-inducing IFN-β (TRIF)-dependent production of type I interferons contributed to IL-1β production by a broad array of Gramnegative bacterial pathogens (Broz et al, 2012;Gurung et al, 2012;Rathinam et al, 2012). In contrast, caspase-11 was dispensable for IL-1β secretion by Gram-positive bacteria.…”

Section: Caspase-11: a Cytosolic Sensor Of Lipopolysaccharidesmentioning

confidence: 99%

“…It is implicated in host defence against a wide range of bacterial (Staphylococcus aureus, Escherichia coli, Citrobacter rodentium) (He et al, 2010;Gurung et al, 2012), viral (influenza A) (Allen et al, 2009;Thomas et al, 2009), fungal (Candida albicans, Aspergillus fumigates; Gross et al, 2009) and parasitic (Leishmania amazonensis) infections (Lamkanfi and Dixit, 2012;Lima et al, 2013). In addition, the Nlrp3 inflammasome is activated by damage-associated molecular patterns (DAMPs) such as adenosine triphosphate (ATP), uric acid crystals, amyloid β fibrils and hyaluronan that are thought to trigger inflammation under sterile conditions.…”

Section: The Nlrp3 Inflammasomementioning

confidence: 99%

Inflammatory caspases: key regulators of inflammation and cell death

Fernández¹,

Lamkanfi²

2014

Biological Chemistry

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Abstract:The innate immune system represents the first line of defence against infectious agents, and co-ordinates cellular and molecular mechanisms that result in effective inflammatory and anti-microbial responses against pathogens. Infection and cellular stress trigger assembly of canonical and noncanonical inflammasome complexes that activate the inflammatory caspases-1 and -11, respectively. These inflammatory caspases play key roles in innate immune responses by inducing pyroptosis to halt intracellular replication of pathogens, and by engaging the extracellular release of pro-inflammatory cytokines and danger signals. In addition, the inflammatory caspases-4, -5 and -11 were recently shown to directly bind microbial components. Although the immune roles of caspase-12 are debated, it was proposed to dampen inflammatory responses by interfering with caspase-1 activation and other innate immune pathways. Here, we recapitulate the reported roles of inflammatory caspases with an emphasis on recent insights into their biological functions.

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“…In addition to the canonical inflammasome, cytosolic LPS or infection by Gramnegative bacteria triggers a caspase-11-containing noncanonical inflammasome (16)(17)(18). This noncanonical inflammasome induces GSDMD-mediated cell death and IL-1␣ secretion independently of caspase-1 in response to caspase-11-mediated sensing of cytosolic LPS (14,15,(19)(20)(21).…”

mentioning

confidence: 99%

Guanylate Binding Proteins Regulate Inflammasome Activation in Response to Hyperinjected Yersinia Translocon Components

et al. 2017

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Gram-negative bacterial pathogens utilize virulence-associated secretion systems to inject, or translocate, effector proteins into host cells to manipulate cellular processes and promote bacterial replication. However, translocated bacterial products are sensed by nucleotide binding domain and leucine-rich repeat-containing proteins (NLRs), which trigger the formation of a multiprotein complex called the inflammasome, leading to secretion of interleukin-1 (IL-1) family cytokines, pyroptosis, and control of pathogen replication. Pathogenic Yersinia bacteria inject effector proteins termed Yops, as well as pore-forming proteins that comprise the translocon itself, into target cells. The Yersinia translocation regulatory protein YopK promotes bacterial virulence by limiting hyperinjection of the translocon proteins YopD and YopB into cells, thereby limiting cellular detection of Yersinia virulence activity. How hyperinjection of translocon proteins leads to inflammasome activation is currently unknown. We found that translocated YopB and YopD colocalized with the late endosomal/lysosomal protein LAMP1 and that the frequency of YopD and LAMP1 association correlated with the level of caspase-1 activation in individual cells. We also observed colocalization between YopD and Galectin-3, an indicator of endosomal membrane damage. Intriguingly, YopK limited the colocalization of Galectin-3 with YopD, suggesting that YopK limits the induction or sensing of endosomal membrane damage by components of the type III secretion system (T3SS) translocon. Furthermore, guanylate binding proteins (GBPs) encoded on chromosome 3 (Gbp Chr3 ), which respond to pathogen-induced damage or alteration of host membranes, were necessary for inflammasome activation in response to hyperinjected YopB/-D. Our findings indicate that lysosomal damage by Yersinia translocon proteins promotes inflammasome activation and implicate GBPs as key regulators of this process.

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Toll or Interleukin-1 Receptor (TIR) Domain-containing Adaptor Inducing Interferon-β (TRIF)-mediated Caspase-11 Protease Production Integrates Toll-like Receptor 4 (TLR4) Protein- and Nlrp3 Inflammasome-mediated Host Defense against Enteropathogens

Cited by 222 publications

References 40 publications

Caspase-11 stimulates rapid flagellin-independent pyroptosis in response to Legionella pneumophila

Caspase-11 stimulates rapid flagellin-independent pyroptosis in response to Legionella pneumophila

Inflammatory caspases: key regulators of inflammation and cell death

Guanylate Binding Proteins Regulate Inflammasome Activation in Response to Hyperinjected Yersinia Translocon Components

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