Next Article in Journal / Special Issue
The Pore-Forming Haemolysins of Bacillus Cereus: A Review
Previous Article in Journal
Limited Stability of Microcystins in Oligopeptide Compositions of Microcystis aeruginosa (Cyanobacteria): Implications in the Definition of Chemotypes
Previous Article in Special Issue
Structure, Function, and Biology of the Enterococcus faecalis Cytolysin
Article Menu

Export Article

Open AccessArticle
Toxins 2013, 5(6), 1105-1118;

Reduction of Streptolysin O (SLO) Pore-Forming Activity Enhances Inflammasome Activation

Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15260, USA
Department of Cell Biology and Physiology, Washington University, St. Louis, MO 63110, USA
Howard Hughes Medical Institute and Rheumatology Division, Department of Medicine, Washington University, St. Louis, MO 63110, USA
Author to whom correspondence should be addressed.
Received: 1 March 2013 / Revised: 29 May 2013 / Accepted: 3 June 2013 / Published: 6 June 2013
(This article belongs to the Special Issue Pore-Forming Toxins)
Full-Text   |   PDF [894 KB, uploaded 24 June 2013]   |  


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 preventing macrophages from successfully repairing their plasma membrane and elaborating more robust cytokine production. We suggest that mutagenesis of pore-forming toxins represents a strategy to enhance adjuvant activity. View Full-Text
Keywords: NLRP3; inflammasome; Caspase-1; plasma membrane repair; streptolysin O NLRP3; inflammasome; Caspase-1; plasma membrane repair; streptolysin O

Figure 1

This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

Share & Cite This Article

MDPI and ACS Style

Keyel, P.A.; Roth, R.; Yokoyama, W.M.; Heuser, J.E.; Salter, R.D. Reduction of Streptolysin O (SLO) Pore-Forming Activity Enhances Inflammasome Activation. Toxins 2013, 5, 1105-1118.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Toxins EISSN 2072-6651 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top