<i>Salmonella</i> Infection Induces Recruitment of Caspase-8 to the Inflammasome To Modulate IL-1β Production

Man, Si Ming; Tourlomousis, Panagiotis; Hopkins, Lee; Monie, Tom P.; Fitzgerald, Katherine A.; Bryant, Clare E.

doi:10.4049/jimmunol.1301581

Cited by 219 publications

(252 citation statements)

References 45 publications

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“…Caspase-8 has also been suggested to regulate NF-κB activity (10,38,39). We found a reduction in TNF and IL-6 release, and pro-IL-1β expression, all controlled by NF-κB, in RIP1 KO, caspase-8 cKO, and RIP3 −/− caspase-8 −/− , but not in RIP3 −/− macrophages upon infection or LPS treatment (Fig.…”

Section: Significancementioning

confidence: 51%

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Caspase-8 and RIP kinases regulate bacteria-induced innate immune responses and cell death

Weng

Marty-Roix

Ganesan

et al. 2014

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

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266

263

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A number of pathogens cause host cell death upon infection, and Yersinia pestis, infamous for its role in large pandemics such as the "Black Death" in medieval Europe, induces considerable cytotoxicity. The rapid killing of macrophages induced by Y. pestis, dependent upon type III secretion system effector Yersinia outer protein J (YopJ), is minimally affected by the absence of caspase-1, caspase-11, Fas ligand, and TNF. Caspase-8 is known to mediate apoptotic death in response to infection with several viruses and to regulate programmed necrosis (necroptosis), but its role in bacterially induced cell death is poorly understood. Here we provide genetic evidence for a receptor-interacting protein (RIP) kinasecaspase-8-dependent macrophage apoptotic death pathway after infection with Y. pestis, influenced by Toll-like receptor 4-TIR-domain-containing adapter-inducing interferon-β (TLR4-TRIF). Interestingly, macrophages lacking either RIP1, or caspase-8 and RIP3, also had reduced infection-induced production of IL-1β, IL-18, TNF, and IL-6; impaired activation of the transcription factor NF-κB; and greatly compromised caspase-1 processing. Cleavage of the proform of caspase-1 is associated with triggering inflammasome activity, which leads to the maturation of IL-1β and IL-18, cytokines important to host responses against Y. pestis and many other infectious agents. Our results identify a RIP1-caspase-8/RIP3-dependent caspase-1 activation pathway after Y. pestis challenge. Mice defective in caspase-8 and RIP3 were also highly susceptible to infection and displayed reduced proinflammatory cytokines and myeloid cell death. We propose that caspase-8 and the RIP kinases are key regulators of macrophage cell death, NF-κB and inflammasome activation, and host resistance after Y. pestis infection.

show abstract

Section: Significancementioning

confidence: 51%

“…The effect on caspase-1 cleavage may be mediated by the inflammasome adaptor ASC (Fig. 5E), because ASC can associate with caspase-8 after Francisella or Salmonella infection (38,48), although the role of ASC may differ depending upon conditions and source of YopJ (16,23,25).…”

Section: Significancementioning

confidence: 99%

Caspase-8 and RIP kinases regulate bacteria-induced innate immune responses and cell death

Weng

Marty-Roix

Ganesan

et al. 2014

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

Self Cite

266

263

View full text Add to dashboard Cite

show abstract

“…For example, caspase-8 has recently been identified to be recruited to the inflammasome to process pro-IL-1b, 79 but the relative contribution of caspase-8 to inflammation processes elicited by CNS injury has not been studied.…”

Section: Inflammasome Activation After Brain and Spinal Cord Injurymentioning

confidence: 99%

Activation and Regulation of Cellular Inflammasomes: Gaps in Our Knowledge for Central Nervous System Injury

Vaccari¹,

Dietrich²,

Keane

2014

J Cereb Blood Flow Metab

292

227

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The inflammasome is an intracellular multiprotein complex involved in the activation of caspase-1 and the processing of the proinflammatory cytokines interleukin-1b (IL-1b) and IL-18. The inflammasome in the central nervous system (CNS) is involved in the generation of an innate immune inflammatory response through IL-1 cytokine release and in cell death through the process of pyroptosis. In this review, we consider the different types of inflammasomes (NLRP1, NLRP2, NLRP3, and AIM2) that have been described in CNS cells, namely neurons, astrocytes, and microglia. Importantly, we focus on the role of the inflammasome after brain and spinal cord injury and cover the potential activators of the inflammasome after CNS injury such as adenosine triphosphate and DNA, and the therapeutic potential of targeting the inflammasome to improve outcomes after CNS trauma.

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“…6,10 Initiation of mitochondrial apoptosis also releases SMAC/DIABLO, which inhibits XIAP and enables caspase-3 to further activate caspase-8. 11 Caspase-8 is also activated downstream of the NLRP3, AIM2 and NLRC4 inflammasomes in response to canonical triggers in macrophages 4,[12][13][14] or downstream of Dectin-1 in dendritic cells. [15][16][17] The activation of caspase-8 in leukocytes requires ASC and regulates the non-canonical maturation of IL-1β.…”

mentioning

confidence: 99%

NLRP3 regulates a non-canonical platform for caspase-8 activation during epithelial cell apoptosis

et al. 2016

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Nod-like receptor, pyrin containing 3 (NLRP3) is characterized primarily as a canonical caspase-1 activating inflammasome in macrophages. NLRP3 is also expressed in the epithelium of the kidney and gut; however, its function remains largely undefined. Primary mouse tubular epithelial cells (TEC) lacking Nlrp3 displayed reduced apoptosis downstream of the tumor necrosis factor (TNF) receptor and CD95. TECs were identified as type II apoptotic cells that activated caspase-8, tBid and mitochondrial apoptosis via caspase-9, responses that were reduced in Nlrp3 − / − cells. The activation of caspase-8 during extrinsic apoptosis induced by TNFα/cycloheximide (TNFα/CHX) was dependent on adaptor protein apoptosis-associated speck-like protein containing a CARD (ASC) and completely independent of caspase-1 or caspase-11. TECs and primary human proximal tubular epithelial cells (HPTC) did not activate a canonical inflammasome, caspase-1, or IL-1β secretion in response to TNFα/CHX or NLRP3-dependent triggers, such as ATP or nigericin. In cell fractionation studies and by confocal microscopy, NLRP3 colocalized with ASC and caspase-8 in speck-like complexes at the mitochondria during apoptosis. The formation of NLRP3/ASC/caspase-8 specks in response to TNFα/ CHX was downstream of TNFR signaling and dependent on potassium efflux. Epithelial ASC specks were present in enteroids undergoing apoptosis and in the injured tubules of wild-type but not Nlrp3 − / − or ASC − / − mice following ureteric unilateral obstruction in vivo. These data show that NLRP3 and ASC form a conserved non-canonical platform for caspase-8 activation, independent of the inflammasome that regulates apoptosis within epithelial cells.

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Salmonella Infection Induces Recruitment of Caspase-8 to the Inflammasome To Modulate IL-1β Production

Cited by 219 publications

References 45 publications

Caspase-8 and RIP kinases regulate bacteria-induced innate immune responses and cell death

Caspase-8 and RIP kinases regulate bacteria-induced innate immune responses and cell death

Activation and Regulation of Cellular Inflammasomes: Gaps in Our Knowledge for Central Nervous System Injury

NLRP3 regulates a non-canonical platform for caspase-8 activation during epithelial cell apoptosis

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