Leukocidin A/B (LukAB) Kills Human Monocytes via Host NLRP3 and ASC when Extracellular, but Not Intracellular

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Staphylococcus aureus infections are becoming increasingly common, aggressive, and difficult to manage clinically. S. aureus produces a number of pore-forming toxins that target and kill immune cells. In this study, we demonstrate that LukAB is primarily responsible for S. aureus-mediated targeting and killing of human monocytes. We show that the NLRP3-ASC inflammasome, a sensor of cell membrane damage and trigger of inflammation, is critical for this response. S. aureus uses LukAB to kill immune cells both through external interactions (LukAB on the cell surface) and through internal interactions (LukAB secretion after S. aureus is engulfed by the immune cell). Interestingly, we show that the mechanism by which LukAB kills immune cells in these two settings differs. This is the first report of a S. aureus toxin manipulating unique immune signaling pathways depending on the cellular site of contact. Understanding the multitude of ways by which S. aureus evades the immune response is critical for our ability to treat infections with this pathogen.

Vyšlo v časopise: Leukocidin A/B (LukAB) Kills Human Monocytes via Host NLRP3 and ASC when Extracellular, but Not Intracellular. PLoS Pathog 11(6): e32767. doi:10.1371/journal.ppat.1004970
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004970

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