Activation of human polymorphonuclear neutrophils by streptolysin O from Streptococcus pyogenes leads to the release of proinflammatory mediators.
Nilsson. Maria M; Sørensen. Ole E OE; Mörgelin. Matthias M; Weineisen. Maria M; Sjöbring. Ulf U; Herwald. Heiko H
Key Findings
- Streptolysin O (SLO) perforates neutrophils, leading to calcium influx and p38 MAPK activation.
- Activated neutrophils release LL‑37, alpha‑defensins, elastase, and heparin‑binding protein.
- The release of these mediators may amplify inflammation and contribute to the severity of S. pyogenes infections.
Practical Outcomes
- For biohackers, the work mainly confirms that LL‑37 is naturally released during bacterial infection, not that taking it as a supplement will boost immunity. It suggests caution: stimulating LL‑37 release via infection can also trigger harmful inflammation. No direct dosing or protocol guidance emerges from this study.
Summary
The study shows that a toxin from the bacteria Streptococcus pyogenes punches holes in human neutrophils, causing a calcium surge and activation of a signaling pathway (p38 MAPK). This triggers the cells to dump out several immune proteins, including the antimicrobial peptide LL‑37, along with other defensins and enzymes that can increase inflammation and leakiness of blood vessels.
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.
Study Information
pubmed
2006
10.1160/th05-08-0572