Reduction of streptolysin O (SLO) pore-forming activity enhances inflammasome activation.

Peter Keyel, Robyn Roth, Wayne M Yokoyama, John E Heuser, Russell D Salter

Research output: Contribution to journalArticle

Abstract

Pore-forming toxins are utilized by bacterial and mammalian cells to exert pathogenic effects and induce cell lysis. In addition to rapid plasma membrane repair, macrophages respond to pore-forming toxins through activation of the NLRP3 inflammasome, leading to IL-1β secretion and pyroptosis. The structural determinants of pore-forming toxins required for NLRP3 activation remain unknown. Here, we demonstrate using streptolysin O (SLO) that pore-formation controls IL-1β secretion and direct toxicity. An SLO mutant incapable of pore-formation did not promote direct killing, pyroptosis or IL-1β production. This indicated that pore formation is necessary for inflammasome activation. However, a partially active mutant (SLO N402C) that was less toxic to macrophages than wild-type SLO, even at concentrations that directly lysed an equivalent number of red blood cells, enhanced IL-1β production but did not alter pyroptosis. This suggests that direct lysis may attenuate immune responses by pre
Original languageEnglish
Pages (from-to)1105-1118
JournalToxins
StatePublished - Jun 6 2013

Fingerprint Dive into the research topics of 'Reduction of streptolysin O (SLO) pore-forming activity enhances inflammasome activation.'. Together they form a unique fingerprint.

  • Cite this

    Keyel, P., Roth, R., Yokoyama, W. M., Heuser, J. E., & Salter, R. D. (2013). Reduction of streptolysin O (SLO) pore-forming activity enhances inflammasome activation. Toxins, 1105-1118.