title: The staphylococcal toxin Panton-Valentine Leukocidin targets human C5a receptors.
abstract: Panton-Valentine Leukocidin (PVL) is a staphylococcal bicomponent pore-forming toxin linked to severe invasive infections. Target-cell and species specificity of PVL are poorly understood, and the mechanism of action of this toxin in Staphylococcus aureus virulence is controversial. Here, we identify the human complement receptors C5aR and C5L2 as host targets of PVL, mediating both toxin binding and cytotoxicity. Expression and interspecies variations of the C5aR determine cell and species specificity of PVL. The C5aR binding PVL component, LukS-PV, is a potent inhibitor of C5a-induced immune cell activation. These findings provide insight into leukocidin function and staphylococcal virulence and offer directions for future investigations into individual susceptibility to severe staphylococcal disease.
authors.affiliation: Medical Microbiology, University Medical Center Utrecht, 3584CX Utrecht, The Netherlands.
authors.forename: András N
authors.initials: AN
authors.lastname: Spaan
authors.affiliation: CIRI, International Center for Infectiology Research, LabEx Ecofect, Université Lyon 1, 69007 Lyon, France; Inserm, U1111, 69007 Lyon, France; Ecole Normale Supérieure de Lyon, 69007 Lyon, France; CNRS, UMR5308, 69007 Lyon, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Henry
authors.affiliation: Medical Microbiology, University Medical Center Utrecht, 3584CX Utrecht, The Netherlands.
authors.forename: Willemien J M
authors.initials: WJM
authors.lastname: van Rooijen
authors.affiliation: CIRI, International Center for Infectiology Research, LabEx Ecofect, Université Lyon 1, 69007 Lyon, France; Inserm, U1111, 69007 Lyon, France; Ecole Normale Supérieure de Lyon, 69007 Lyon, France; CNRS, UMR5308, 69007 Lyon, France.
authors.forename: Magali
authors.initials: M
authors.lastname: Perret
authors.affiliation: CIRI, International Center for Infectiology Research, LabEx Ecofect, Université Lyon 1, 69007 Lyon, France; Inserm, U1111, 69007 Lyon, France; Ecole Normale Supérieure de Lyon, 69007 Lyon, France; CNRS, UMR5308, 69007 Lyon, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Badiou
authors.affiliation: Medical Microbiology, University Medical Center Utrecht, 3584CX Utrecht, The Netherlands.
authors.forename: Piet C
authors.initials: PC
authors.lastname: Aerts
authors.affiliation: Medicinal Chemistry and Chemical Biology, Utrecht University, 3584CX Utrecht, The Netherlands.
authors.forename: Johan
authors.initials: J
authors.lastname: Kemmink
authors.affiliation: Medical Microbiology, University Medical Center Utrecht, 3584CX Utrecht, The Netherlands.
authors.forename: Carla J C
authors.initials: CJC
authors.lastname: de Haas
authors.affiliation: Medical Microbiology, University Medical Center Utrecht, 3584CX Utrecht, The Netherlands.
authors.forename: Kok P M
authors.initials: KPM
authors.lastname: van Kessel
authors.affiliation: CIRI, International Center for Infectiology Research, LabEx Ecofect, Université Lyon 1, 69007 Lyon, France; Inserm, U1111, 69007 Lyon, France; Ecole Normale Supérieure de Lyon, 69007 Lyon, France; CNRS, UMR5308, 69007 Lyon, France; Hospices Civils de Lyon, 69007 Lyon, France.
authors.forename: François
authors.initials: F
authors.lastname: Vandenesch
authors.affiliation: CIRI, International Center for Infectiology Research, LabEx Ecofect, Université Lyon 1, 69007 Lyon, France; Inserm, U1111, 69007 Lyon, France; Ecole Normale Supérieure de Lyon, 69007 Lyon, France; CNRS, UMR5308, 69007 Lyon, France; Hospices Civils de Lyon, 69007 Lyon, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Lina
authors.affiliation: Medical Microbiology, University Medical Center Utrecht, 3584CX Utrecht, The Netherlands. Electronic address: j.vanstrijp@umcutrecht.nl.
authors.forename: Jos A G
authors.initials: JAG
authors.lastname: van Strijp
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism; D001427:Bacterial Toxins / Q000378:metabolism* / Q000633:toxicity; D002478:Cells, Cultured; D005098:Exotoxins / Q000378:metabolism* / Q000633:toxicity; D054884:Host-Pathogen Interactions; D006801:Humans; D007956:Leukocidins / Q000378:metabolism* / Q000633:toxicity; D044087:Receptor, Anaphylatoxin C5a / Q000378:metabolism*; D019707:Receptors, Chemokine / Q000378:metabolism; D013211:Staphylococcus aureus / Q000276:immunology* / Q000472:pathogenicity*
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; C417003:C5aR2 protein, human; D005098:Exotoxins; D007956:Leukocidins; C078284:Panton-Valentine leukocidin; D044087:Receptor, Anaphylatoxin C5a; D019707:Receptors, Chemokine; C108483:leukocidin S-component protein, Staphylococcus