title: Staphylococcus aureus-dependent septic arthritis in murine knee joints: local immune response and beneficial effects of vaccination.
abstract: Staphylococcus aureus is the major cause of human septic arthritis and osteomyelitis, which deserve special attention due to their rapid evolution and resistance to treatment. The progression of the disease depends on both bacterial presence in situ and uncontrolled disruptive immune response, which is responsible for chronic disease. Articular and bone infections are often the result of blood bacteremia, with the knees and hips being the most frequently infected joints showing the worst clinical outcome. We report the development of a hematogenous model of septic arthritis in murine knees, which progresses from an acute to a chronic phase, similarly to what occurs in humans. Characterization of the local and systemic inflammatory and immune responses following bacterial infection brought to light specific signatures of disease. Immunization of mice with the vaccine formulation we have recently described (4C-Staph), induced a strong antibody response and specific CD4+ effector memory T cells, and resulted in reduced bacterial load in the knee joints, a milder general inflammatory state and protection against bacterial-mediated cellular toxicity. Possible correlates of protection are finally proposed, which might contribute to the development of an effective vaccine for human use.
authors.affiliation: GSK Vaccines, Via Fiorentina 1, Siena, 53100, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Corrado
authors.affiliation: GSK Vaccines, Via Fiorentina 1, Siena, 53100, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Donato
authors.affiliation: GSK Vaccines, Via Fiorentina 1, Siena, 53100, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Maccari
authors.affiliation: GSK Vaccines, Via Fiorentina 1, Siena, 53100, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Cecchi
authors.affiliation: GSK Vaccines, Via Fiorentina 1, Siena, 53100, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Spadafina
authors.affiliation: GSK Vaccines, Via Fiorentina 1, Siena, 53100, Italy.
authors.forename: Letizia
authors.initials: L
authors.lastname: Arcidiacono
authors.affiliation: GSK Vaccines, Via Fiorentina 1, Siena, 53100, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Tavarini
authors.affiliation: GSK Vaccines, Via Fiorentina 1, Siena, 53100, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Sammicheli
authors.affiliation: GSK Vaccines, Via Fiorentina 1, Siena, 53100, Italy.
authors.forename: Donatello
authors.initials: D
authors.lastname: Laera
authors.affiliation: GSK Vaccines, Via Fiorentina 1, Siena, 53100, Italy.
authors.forename: Andrea Guido Oreste
authors.initials: AG
authors.lastname: Manetti
authors.affiliation: GSK Vaccines, Via Fiorentina 1, Siena, 53100, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Ruggiero
authors.affiliation: GSK Vaccines, Via Fiorentina 1, Siena, 53100, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Galletti
authors.affiliation: GSK Vaccines, Via Fiorentina 1, Siena, 53100, Italy.
authors.forename: Sandra
authors.initials: S
authors.lastname: Nuti
authors.affiliation: GSK Vaccines, Via Fiorentina 1, Siena, 53100, Italy.
authors.forename: Ennio
authors.initials: E
authors.lastname: De Gregorio
authors.affiliation: GSK Vaccines, Via Fiorentina 1, Siena, 53100, Italy.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Bertholet
authors.affiliation: GSK Vaccines, Via Fiorentina 1, Siena, 53100, Italy.
authors.forename: Anja
authors.initials: A
authors.lastname: Seubert
authors.affiliation: GSK Vaccines, Via Fiorentina 1, Siena, 53100, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Bagnoli
authors.affiliation: GSK Vaccines, Via Fiorentina 1, Siena, 53100, Italy.
authors.forename: Giuliano
authors.initials: G
authors.lastname: Bensi
authors.affiliation: GSK Vaccines, Via Fiorentina 1, Siena, 53100, Italy.
authors.forename: Emiliano
authors.initials: E
authors.lastname: Chiarot
mesh_terms: D000818:Animals; D001170:Arthritis, Infectious / Q000276:immunology / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control; D005260:Female; D007719:Knee Joint / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D051379:Mice; D013203:Staphylococcal Infections / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D013209:Staphylococcal Vaccines / Q000276:immunology / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000276:immunology*; D014611:Vaccination
chemical_list: D013209:Staphylococcal Vaccines