Interferons Increase Cell Resistance to Staphylococcal Alpha-Toxin

Yarovinsky, Timur O.; Monick, Martha M.; Husmann, Matthias; Hunninghake, Gary W.

doi:10.1128/iai.01088-07

Cited by 17 publications

(12 citation statements)

References 45 publications

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“…Pretreatment of human FS-4 fibroblasts with IL-1␤ inhibits the IFN␤ production that normally occurs in response to poly(I:C) stimulation (38). In addition, pretreatment with IFN␣ inhibited the secretion of IL-1␤ that normally occurs in response to Staphylococcal ␣-toxin (39).…”

Section: Discussionmentioning

confidence: 99%

Active Caspase-1-Mediated Secretion of Retinoic Acid Inducible Gene-I

Kim

Yoo

2008

The Journal of Immunology

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Caspase-1 is an inflammatory caspase that controls the activation and secretion of the inflammatory cytokines, IL-1β and IL-18. We observed that cellular levels of retinoic acid-inducible gene-I (RIG-I) were enhanced when the pan-caspase inhibitor Z-VAD-fmk or caspase-1-specific inhibitor Z-WEHD-fmk blocked caspase activity. Overexpression of caspase-1 reduced cellular levels of RIG-I and inhibited RIG-I-mediated signaling activity. Enzymatic activity of caspase-1 was necessary to control RIG-I, although it was not a substrate of proteolytic cleavage by caspase-1. Caspase-1 physically interacted with full length RIG-I, but not with mutant forms lacking either the amino- or carboxyl-terminal domains. RIG-I was present in the supernatant of cells transfected with active caspase-1 but not with caspase-4. Stimulating cells with LPS and ATP also induced secretion of endogenous RIG-I in macrophages. Our data suggest a novel mechanism that negatively regulates RIG-I-mediated signaling activity via caspase-1-dependent secretion of RIG-I protein.

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Section: Discussionmentioning

confidence: 99%

Active Caspase-1-Mediated Secretion of Retinoic Acid Inducible Gene-I

Kim

Yoo

2008

The Journal of Immunology

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“…In the light of the observations presented here, inhibition of P2 receptors is a α-toxin-induced cytotoxicity. α-Toxin is known to provoke significant reduction of the intracellular ATP concentration in various cell types such as monocytes [7,42], jurkat cells [13] and human lung epithelial cells [7,42]. This profound reduction is mostly caused by ATP release to the exterior.…”

Section: Atp (Mm)mentioning

confidence: 99%

Haemolysis induced by α-toxin from Staphylococcus aureus requires P2X receptor activation

Skals

Leipziger

Praetorius

2011

Pflugers Arch - Eur J Physiol

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Recently, it was documented that α-haemolysin (HlyA) from Escherichia coli uses erythrocyte P2 receptors cause lysis. This finding was surprising as it appeared firmly established that HlyA-dependent pore formation per se is sufficient for full cell lysis. We discovered that HlyA induced a sequential process of shrinkage and swelling and that the final haemolysis is completely prevented by blockers of P2X receptors and pannexin channels. This finding has potential clinical relevance as it may offer specific pharmacological interference to ameliorate haemolysis inflicted by pore-forming bacterial toxins. In this context, it is essential to know whether this is specific to HlyA-induced cell damage or if other bacterial pore-forming toxins involve purinergic signals to orchestrate haemolysis. Here, we investigate if the haemolysis produced by α-toxin from Staphylococcus aureus involves P2 receptor activation. We observed that α-toxin-induced haemolysis is completely blocked by the unselective P2 receptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid. Moreover, several selective blockers of P2X(1) and P2X(7) ionotropic receptors abolished haemolysis in murine and equine erythrocytes. Inhibitors of pannexin channels partially reduced the α-toxin induced lysis. Thus, we conclude that α-toxin, similar to HlyA from E. coli produces cell damage by specific activation of a purinergic signalling cascade. These data indicate that pore-forming toxins in general require purinergic signalling to elicit their toxicity.

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“…The discovery of ADAM10 as a cellular receptor for α-toxin has allowed for a more thorough examination of the molecular mechanisms by which α-toxin contributes to disease at the epithelial and endothelial tissue barriers [11,12,13]. These findings, along with substantial recent advances in our understanding of toxin-mediated regulation of host immunity [9,29,31,125,126,127,128], will be the subject of this section.…”

Section: Contribution Of α-Toxin To S Aureus Diseasementioning

confidence: 99%

“…Further, type-I interferon (IFN) produced by the host can afford protection against toxin-induced injury [126]. This effect is dependent on the presence of phospholipid scramblase I (PLSCR1), which provides protection against cellular leakage of ATP [128].…”

Section: Contribution Of α-Toxin To S Aureus Diseasementioning

confidence: 99%

Staphylococcus aureus α-Toxin: Nearly a Century of Intrigue

Berube

Wardenburg

2013

Toxins

527

464

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Staphylococcus aureus secretes a number of host-injurious toxins, among the most prominent of which is the small β-barrel pore-forming toxin α-hemolysin. Initially named based on its properties as a red blood cell lytic toxin, early studies suggested a far greater complexity of α-hemolysin action as nucleated cells also exhibited distinct responses to intoxication. The hemolysin, most aptly referred to as α-toxin based on its broad range of cellular specificity, has long been recognized as an important cause of injury in the context of both skin necrosis and lethal infection. The recent identification of ADAM10 as a cellular receptor for α-toxin has provided keen insight on the biology of toxin action during disease pathogenesis, demonstrating the molecular mechanisms by which the toxin causes tissue barrier disruption at host interfaces lined by epithelial or endothelial cells. This review highlights both the historical studies that laid the groundwork for nearly a century of research on α-toxin and key findings on the structural and functional biology of the toxin, in addition to discussing emerging observations that have significantly expanded our understanding of this toxin in S. aureus disease. The identification of ADAM10 as a proteinaceous receptor for the toxin not only provides a greater appreciation of truths uncovered by many historic studies, but now affords the opportunity to more extensively probe and understand the role of α-toxin in modulation of the complex interaction of S. aureus with its human host.

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Interferons Increase Cell Resistance to Staphylococcal Alpha-Toxin

Cited by 17 publications

References 45 publications

Active Caspase-1-Mediated Secretion of Retinoic Acid Inducible Gene-I

Active Caspase-1-Mediated Secretion of Retinoic Acid Inducible Gene-I

Haemolysis induced by α-toxin from Staphylococcus aureus requires P2X receptor activation

Staphylococcus aureus α-Toxin: Nearly a Century of Intrigue

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