Proteomics

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Neutrophils from patients with recurring Panton-Valentine Leukocidin-positive Staphylococcus aureus infections are more sensitive to PVL induced NETosis


ABSTRACT: Panton-Valentine Leukocidin (PVL) is a Staphylococcus aureus toxin that binds to and kills human neutrophils resulting in the formation of neutrophil extracellular traps. A subset of individuals colonized with PVL expressing S. aureus suffer from recurring infections. We found that neutrophils from affected individuals display increased spontaneous NET formation after isolation, and increased sensitivity to killing by PVL. Compared to healthy controls, the expression of the target receptors for PVL, CD45 and C5L2, but not CD88, was increased in these patients, and the expression correlated to the amount of PVL-induced NETs produced. NADPH-oxidase activity was not important for PVL induced NETosis as neutrophils from CGD patients produced NETs in response to PVL. Through NET proteome analysis we identified that the protein content of PVL induced NETs is different from mitogen induced NETs. The abundance of the antimicrobial proteins LL37, myeloperoxidase, azurocidin, and proteinase 3 was lower on PVL NETs and PVL-induced NETs were deficient in killing Staphylococcus aureus. Neutrophils from patients that suffer from recurring PVL-positive infections may be more sensitive to PVL-induced NETosis, impairing their ability to combat the infection.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Christian Frese  

LAB HEAD: Christian Karl Frese

PROVIDER: PXD025702 | Pride | 2023-11-23

REPOSITORIES: Pride

Dataset's files

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QE1_191113_19M031_.msf Msf
QE1_191113_19M031_1_1.raw Raw
QE1_191113_19M031_1_2.raw Raw
QE1_191113_19M031_1_3.raw Raw
QE1_191113_19M031_1_4.raw Raw
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Publications

Panton-Valentine leukocidin-induced neutrophil extracellular traps lack antimicrobial activity and are readily induced in patients with recurrent PVL + -Staphylococcus aureus infections.

Jhelum Hina H   Čerina Dora D   Harbort C J CJ   Lindner Andreas A   Hanitsch Leif Gunnar LG   Leistner Rasmus R   Schröder Jennyver-Tabea JT   von Bernuth Horst H   Stegemann Miriam Songa MS   Schürmann Mariana M   Zychlinsky Arturo A   Krüger Renate R   Marsman Gerben G  

Journal of leukocyte biology 20240101 2


Staphylococcus aureus strains that produce the toxin Panton-Valentine leukocidin (PVL-SA) frequently cause recurrent skin and soft tissue infections. PVL binds to and kills human neutrophils, resulting in the formation of neutrophil extracellular traps (NETs), but the pathomechanism has not been extensively studied. Furthermore, it is unclear why some individuals colonized with PVL-SA experience recurring infections whereas others are asymptomatic. We thus aimed to (1) investigate how PVL exerts  ...[more]

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