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Updated: Aug 8, 2026

Implementation of a Permeable Membrane Insert-based Infection System to Study the Effects of Secreted Bacterial Toxins on Mammalian Host Cells
Published on: August 19, 2016
Activation of human polymorphonuclear neutrophils by streptolysin O from Streptococcus pyogenes leads to the release
Maria Nilsson1, Ole E Sørensen, Matthias Mörgelin
1Department of Clinical Sciences, Section for Clinical and Experimental Infection Medicine, BMC, B14, Lund University, Tornavägen 10, SE-221 84 Lund, Sweden.
Abstract:
Streptococcus pyogenes is an important Gram-positive pathogen that is strictly limited to infections in humans. Here we report that streptolysin O (SLO), a cytolytic exotoxin secreted by S. pyogenes, activates human polymorphonuclear neutrophils (PMNs) by perforating these cells. This appears to be followed by an influx of Ca(2+) and p38 MAPK activation. As a consequence, PMNs secrete heparin-binding protein, a potent inducer of vascular leakage, and neutrophil-borne proteins, including LL-37, alpha-defensins, and elastase. The results of the present work therefore suggest that the interaction between SLO and PMNs evokes an exaggerated host response which may contribute to the pathogenesis of local and generalized S. pyogenes infections.
Insights
Streptolysin O (SLO) from Streptococcus pyogenes perforates human neutrophils (PMNs), triggering an exaggerated host response. This interaction may drive the pathogenesis of S. pyogenes infections.
Area of Science:
- Immunology
- Microbiology
- Pathogenesis
Background:
- Streptococcus pyogenes is a significant human pathogen.
- Neutrophils play a critical role in host defense against bacterial infections.
Purpose of the Study:
- To investigate the mechanism by which streptolysin O (SLO) from S. pyogenes interacts with and activates human polymorphonuclear neutrophils (PMNs).
- To elucidate the downstream consequences of SLO-induced PMN activation in the context of S. pyogenes infection.
Main Methods:
- Exposure of human PMNs to purified streptolysin O (SLO).
- Assessment of cell viability, calcium influx, and p38 MAPK activation.
- Analysis of secreted neutrophil-borne proteins.
Main Results:
- SLO directly perforates human PMNs, leading to cell activation.
- Activated PMNs exhibit calcium influx and p38 MAPK pathway activation.
- PMNs secrete heparin-binding protein, LL-37, alpha-defensins, and elastase following SLO exposure.
Conclusions:
- SLO-induced PMN activation results in the release of potent inflammatory mediators.
- This exaggerated host response mediated by SLO and PMNs may contribute to the pathogenesis of S. pyogenes infections.
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