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Updated: May 22, 2026
Quantifying the Cytotoxicity of Staphylococcus aureus Against Human Polymorphonuclear Leukocytes
Published on: January 3, 2020
Sublytic concentrations of Staphylococcus aureus Panton-Valentine leukocidin alter human PMN gene expression and
Shawna F Graves1, Scott D Kobayashi, Kevin R Braughton
1Laboratory of Bacterial Pathogenesis, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.
Abstract:
CA-MRSA infections are often caused by strains encoding PVL, which can cause lysis of PMNs and other myeloid cells in vitro, a function considered widely as the primary means by which PVL might contribute to disease. However, at sublytic concentrations, PVL can function as a PMN agonist. To better understand this phenomenon, we investigated the ability of PVL to alter human PMN function. PMNs exposed to PVL had enhanced capacity to produce O(2)(-) in response to fMLF, but unlike priming by LPS, this response did not require TLR signal transduction. On the other hand, there was subcellular redistribution of NADPH oxidase components in PMNs following exposure of these cells to PVL--a finding consistent with priming. Importantly, PMNs primed with PVL had an enhanced ability to bind/ingest and kill Staphylococcus aureus. Priming of PMNs with other agonists, such as IL-8 or GM-CSF, altered the ability of PVL to cause formation of pores in the plasma membranes of these cells. Microarray analysis revealed significant changes in the human PMN transcriptome following exposure to PVL, including up-regulation of molecules that regulate the inflammatory response. Consistent with the microarray data, mediators of the inflammatory response were released from PMNs after stimulation with PVL. We conclude that exposure of human PMNs to sublytic concentrations of PVL elicits a proinflammatory response that is regulated in part at the level of gene expression. We propose that PVL-mediated priming of PMNs enhances the host innate immune response.
Insights
Panton-valentine leukocidin (PVL) at low concentrations primes human neutrophils (PMNs), enhancing their ability to fight Staphylococcus aureus infections. This priming involves gene expression changes and boosts the innate immune response.
Area of Science:
- Microbiology
- Immunology
- Molecular Biology
Background:
- Community-associated Methicillin-resistant Staphylococcus aureus (CA-MRSA) infections are frequently linked to Panton-valentine leukocidin (PVL).
- PVL is known to lyse myeloid cells, but its role as a neutrophil agonist at sublytic concentrations was less understood.
- Understanding PVL's interaction with neutrophils is crucial for deciphering its role in staphylococcal pathogenesis.
Purpose of the Study:
- To investigate how sublytic concentrations of PVL affect human neutrophil (PMN) function.
- To elucidate the molecular mechanisms underlying PVL-mediated neutrophil activation and response.
- To determine if PVL priming enhances neutrophil's capacity to combat Staphylococcus aureus.
Main Methods:
- Exposure of human neutrophils to sublytic concentrations of PVL.
- Assessment of neutrophil oxidative burst (O(2)(-)) and NADPH oxidase component localization.
- Evaluation of neutrophil interaction with and killing of Staphylococcus aureus.
- Microarray analysis of the neutrophil transcriptome following PVL exposure.
- Measurement of inflammatory mediator release from PVL-stimulated neutrophils.
Main Results:
- PVL exposure enhanced neutrophil O(2)(-) production and promoted subcellular redistribution of NADPH oxidase components, indicating priming.
- PVL-primed neutrophils demonstrated improved binding, ingestion, and killing of Staphylococcus aureus.
- Microarray analysis revealed PVL-induced changes in the neutrophil transcriptome, including upregulation of inflammatory response genes.
- PVL stimulation led to the release of inflammatory mediators from neutrophils.
Conclusions:
- Sublytic concentrations of PVL induce a proinflammatory response in human neutrophils, partly regulated by gene expression.
- PVL-mediated neutrophil priming enhances the host's innate immune response against Staphylococcus aureus.
- This study reveals a novel function of PVL as a neutrophil agonist, contributing to host defense mechanisms.
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