title: Dual impact of live Staphylococcus aureus on the osteoclast lineage, leading to increased bone resorption.
abstract: BACKGROUND
  Bone and joint infection, mainly caused by Staphylococcus aureus, is associated with significant morbidity and mortality, characterized by severe inflammation and progressive bone destruction. Studies mostly focused on the interaction between S. aureus and osteoblasts, the bone matrix-forming cells, while interactions between S. aureus and osteoclasts, the only cells known to be able to degrade bone, have been poorly explored.
  
  
  METHODS
  We developed an in vitro infection model of primary murine osteoclasts to study the direct impact of live S. aureus on osteoclastogenesis and osteoclast resorption activity.
  
  
  RESULTS
  Staphylococcal infection of bone marrow-derived osteoclast precursors induced their differentiation into activated macrophages that actively secreted proinflammatory cytokines. These cytokines enhanced the bone resorption capacity of uninfected mature osteoclasts and promoted osteoclastogenesis of the uninfected precursors at the site of infection. Moreover, infection of mature osteoclasts by live S. aureus directly enhanced their ability to resorb bone by promoting cellular fusion.
  
  
  CONCLUSIONS
  Our results highlighted two complementary mechanisms involved in bone loss during bone and joint infection, suggesting that osteoclasts could be a pivotal target for limiting bone destruction.
authors.affiliation: Hospices Civils de Lyon CIRI, International Center for Infectiology Research, University of Lyon Inserm U1111 Ecole Normale Supérieure de Lyon University of Lyon 1 CNRS, UMR5308.
authors.forename: Sophie
authors.initials: S
authors.lastname: Trouillet-Assant
authors.affiliation: Ecole Normale Supérieure de Lyon University of Lyon 1 CNRS, UMR5308 Institut de Génomique Fonctionnelle de Lyon, France.
authors.forename: Marlène
authors.initials: M
authors.lastname: Gallet
authors.affiliation: Ecole Normale Supérieure de Lyon University of Lyon 1 CNRS, UMR5308 Institut de Génomique Fonctionnelle de Lyon, France.
authors.forename: Pauline
authors.initials: P
authors.lastname: Nauroy
authors.affiliation: Hospices Civils de Lyon CIRI, International Center for Infectiology Research, University of Lyon Inserm U1111 Ecole Normale Supérieure de Lyon University of Lyon 1 CNRS, UMR5308.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Rasigade
authors.affiliation: Hospices Civils de Lyon CIRI, International Center for Infectiology Research, University of Lyon Inserm U1111 Ecole Normale Supérieure de Lyon University of Lyon 1 CNRS, UMR5308.
authors.forename: Sacha
authors.initials: S
authors.lastname: Flammier
authors.affiliation: CIRI, International Center for Infectiology Research, University of Lyon Inserm U1111 Ecole Normale Supérieure de Lyon University of Lyon 1 CNRS, UMR5308.
authors.forename: Peggy
authors.initials: P
authors.lastname: Parroche
authors.affiliation: CIRI, International Center for Infectiology Research, University of Lyon Inserm U1111 Ecole Normale Supérieure de Lyon University of Lyon 1 CNRS, UMR5308.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Marvel
authors.affiliation: Hospices Civils de Lyon CIRI, International Center for Infectiology Research, University of Lyon Inserm U1111 Ecole Normale Supérieure de Lyon University of Lyon 1 CNRS, UMR5308.
authors.forename: Tristan
authors.initials: T
authors.lastname: Ferry
authors.affiliation: Hospices Civils de Lyon CIRI, International Center for Infectiology Research, University of Lyon Inserm U1111 Ecole Normale Supérieure de Lyon University of Lyon 1 CNRS, UMR5308.
authors.forename: Francois
authors.initials: F
authors.lastname: Vandenesch
authors.affiliation: Ecole Normale Supérieure de Lyon University of Lyon 1 CNRS, UMR5308 Institut de Génomique Fonctionnelle de Lyon, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Jurdic
authors.affiliation: Hospices Civils de Lyon CIRI, International Center for Infectiology Research, University of Lyon Inserm U1111 Ecole Normale Supérieure de Lyon University of Lyon 1 CNRS, UMR5308.
authors.forename: Frederic
authors.initials: F
authors.lastname: Laurent
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001862:Bone Resorption / Q000382:microbiology*; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D017886:Durapatite; D054884:Host-Pathogen Interactions / Q000502:physiology*; D051379:Mice; D008954:Models, Biological; D010010:Osteoclasts / Q000382:microbiology* / Q000502:physiology*; D013203:Staphylococcal Infections / Q000382:microbiology; D013211:Staphylococcus aureus / Q000235:genetics / Q000472:pathogenicity*
chemical_list: D018829:Adhesins, Bacterial; D016207:Cytokines; C078635:fibronectin-binding proteins, bacterial; D017886:Durapatite
keywords: Staphylococcus aureus; bone and joint infections; osteoclastogenesis; resorption