Panton-Valentine Leukocidin Induces Cytokine Release and Cytotoxicity Mediated by the C5a Receptor on Rabbit Alveolar Macrophages

• Published in: Japanese Journal of Infectious Diseases Vol. 74; no. 4; pp. 352 - 358
• Main Authors: Harada, Shinya, Kawada, Hayato, Maehana, Shotaro, Matsui, Hidehito, Kubo, Makoto, Kojima, Fumiaki, Kitasato, Hidero, Katagiri, Masato
• Format: Journal Article
• Language: English
• Published: Japan National Institute of Infectious Diseases, Japanese Journal of Infectious Diseases Editorial Committee 31.07.2021; Japan Science and Technology Agency
• Subjects: Alveoli; C5a receptor; Cytokines; Cytotoxicity; Drug resistance; Inflammation; Innate immunity; Leukocidin; Macrophages; Methicillin; methicillin-resistant Staphylococcus aureus; necrotizing pneumonia; Panton-Valentine leucocidin; Pneumonia; primary cultured alveolar macrophages; Public health; Rabbits; Receptors; Staphylococcus aureus; Staphylococcus infections; Toxicity; Toxins; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Panton-Valentine leukocidin; Necrotizing pneumonia; C5a receptor; Primary cultured alveolar macrophages; Methicillin-resistant Staphylococcus aureus
• ISSN: 1344-6304; 1884-2836
• DOI: 10.7883/yoken.JJID.2020.657

Necrotizing pneumonia caused by Panton-Valentine leukocidin (PVL)-positive community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) has high mortality rates and is currently a serious clinical issue. PVL is a two-component toxin (LukS-PV and LukF-PV). It can cause necrosis in target cells by forming pores consisting of an octamer comprised of LukS-PV and LukF-PV. However, considering the specificity of PVL towards several target cells and species, the specific effect of PVL remains controversial. Therefore, we focused on necrotizing pneumonia caused by PVL-positive S. aureus and clarified the effect of PVL on alveolar macrophages, which play a central role in innate immunity in the alveolar space. We constructed recombinant PVL (rPVL) components and stimulated alveolar macrophages isolated from rabbits to evaluate cytotoxicity and pro-inflammatory cytokine release. Recombinant LukS-PV (rLukS-PV), but not recombinant LukF-PV (rLukF-PV), induced pro-inflammatory cytokine release. Specifically, tumor necrosis factor (TNF)-α release was mediated by the C5a receptor (C5aR) expressed on rabbit alveolar macrophages, and the toxicity of rPVL, consisting of rLukS-PV and rLukF-PV, towards rabbit alveolar macrophages was mediated by the same receptor. Overall, our findings shed light on the C5aR-mediated cytotoxic effect of PVL on alveolar macrophages, which may be useful for understanding the mechanism of necrotizing pneumonia caused by PVL.