title: Human Monocyte-Derived Osteoclasts Are Targeted by Staphylococcal Pore-Forming Toxins and Superantigens.
abstract: Staphylococcus aureus is the leading cause of bone and joint infections (BJIs). Staphylococcal pathogenesis involves numerous virulence factors including secreted toxins such as pore-forming toxins (PFTs) and superantigens. The role of these toxins on BJI outcome is largely unknown. In particular, few studies have examined how osteoclasts, the bone-resorbing cells, respond to exposure to staphylococcal PFTs and superantigens. We investigated the direct impact of recombinant staphylococcal toxins on human primary mature monocyte-derived osteoclasts, in terms of cytotoxicity and cell activation with cell death and bone resorption assays, using macrophages of the corresponding donors as a reference. Monocyte-derived osteoclasts displayed similar toxin susceptibility profiles compared to macrophages. Specifically, we demonstrated that the Panton-Valentine leukocidin, known as one of the most powerful PFT which lyses myeloid cells after binding to the C5a receptor, was able to induce the death of osteoclasts. The archetypal superantigen TSST-1 was not cytotoxic but enhanced the bone resorption activity of osteoclasts, suggesting a novel mechanism by which superantigen-producing S. aureus can accelerate the destruction of bone tissue during BJI. Altogether, our data indicate that the diverse clinical presentations of BJIs could be related, at least partly, to the toxin profiles of S. aureus isolates involved in these severe infections.
authors.affiliation: Centre International de Recherche en Infectiologie, INSERM U1111, Pathogenesis of staphylococcal infections, University of Lyon 1, Department of Clinical Microbiology, Northern Hospital Group, Hospices Civils de Lyon, 103 grande rue de la Croix Rousse, 69004 Lyon, France.
authors.forename: Sacha
authors.initials: S
authors.lastname: Flammier
authors.affiliation: Centre International de Recherche en Infectiologie, INSERM U1111, Pathogenesis of staphylococcal infections, University of Lyon 1, Department of Clinical Microbiology, Northern Hospital Group, Hospices Civils de Lyon, 103 grande rue de la Croix Rousse, 69004 Lyon, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Rasigade
authors.affiliation: Centre International de Recherche en Infectiologie, INSERM U1111, Pathogenesis of staphylococcal infections, University of Lyon 1, Department of Clinical Microbiology, Northern Hospital Group, Hospices Civils de Lyon, 103 grande rue de la Croix Rousse, 69004 Lyon, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Badiou
authors.affiliation: Centre International de Recherche en Infectiologie, INSERM U1111, Inflammasome, bacterial infections and autoinflammatory diseases, University of Lyon 1, 21 avenue Tony Garnier, 69365 Lyon cedex 07, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Henry
authors.affiliation: Centre International de Recherche en Infectiologie, INSERM U1111, Pathogenesis of staphylococcal infections, University of Lyon 1, Department of Clinical Microbiology, Northern Hospital Group, Hospices Civils de Lyon, 103 grande rue de la Croix Rousse, 69004 Lyon, France.
authors.forename: François
authors.initials: F
authors.lastname: Vandenesch
authors.affiliation: Centre International de Recherche en Infectiologie, INSERM U1111, Pathogenesis of staphylococcal infections, University of Lyon 1, Department of Clinical Microbiology, Northern Hospital Group, Hospices Civils de Lyon, 103 grande rue de la Croix Rousse, 69004 Lyon, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Laurent
authors.affiliation: Centre International de Recherche en Infectiologie, INSERM U1111, Pathogenesis of staphylococcal infections, University of Lyon 1, Department of Clinical Microbiology, Northern Hospital Group, Hospices Civils de Lyon, 103 grande rue de la Croix Rousse, 69004 Lyon, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Trouillet-Assant
mesh_terms: D001427:Bacterial Toxins / Q000378:metabolism*; D001862:Bone Resorption / Q000150:complications / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D002478:Cells, Cultured; D004768:Enterotoxins / Q000378:metabolism*; D005098:Exotoxins / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D007956:Leukocidins / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D010010:Osteoclasts / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D013203:Staphylococcal Infections / Q000150:complications / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D013211:Staphylococcus aureus / Q000502:physiology*; D018089:Superantigens / Q000378:metabolism*
chemical_list: D001427:Bacterial Toxins; D004768:Enterotoxins; D005098:Exotoxins; D007956:Leukocidins; C078284:Panton-Valentine leukocidin; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal