Panton-Valentine leukocidin induces cytokine release and cytotoxicity mediated by the C5a receptor on rabbit alveolar macrophages

Jpn J Infect Dis. 2021 Jan 29. doi: 10.7883/yoken.JJID.2020.657. Online ahead of print.ABSTRACTNecrotizing pneumonia caused by Panton-Valentine leukocidin (PVL)-positive community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) has high mortality, and is currently a serious clinical issue. PVL is a two-component toxin consisting of LukS-PV and LukF-PV. PVL was shown to cause necrosis in target cells by forming pores consisting of an octamer comprised of LukS-PV and LukF-PV. However, because of the specificity of PVL toward several target cells and species, the detailed action of PVL remains controversial. Therefore, we focused on necrotizing pneumonia caused by PVL-positive Staphylococcus aureus and clarified the effects 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, and then evaluated the cytotoxicity and pro-inflammatory cytokine release. Recombinant LukS-PV (rLukS-PV), but not recombinant LukF-PV (rLukF-PV), induced pro-inflammatory cytokine release. Especially, TNF-α release was mediated via the C5a receptor (C5aR) expressed in rabbit alveolar macrophages and rPVL, consisting of rLukS-PV and rLukF-PV, was highly toxic to rabbit alveolar macrophages via the same receptor. Our results, which reveal the action of PVL via C5aR on alveolar macrophages, may be useful for understanding the mechanism of ne...
Source: Japanese Journal of Infectious Diseases - Category: Infectious Diseases Authors: Source Type: research