Staphylococcus aureus-dependent septic arthritis in murine knee joints: local immune response and beneficial effects of vaccination

• Published in: Scientific reports Vol. 6; no. 1; p. 38043
• Main Authors: Corrado, Alessia, Donato, Paolo, Maccari, Silvia, Cecchi, Raffaella, Spadafina, Tiziana, Arcidiacono, Letizia, Tavarini, Simona, Sammicheli, Chiara, Laera, Donatello, Manetti, Andrea Guido Oreste, Ruggiero, Paolo, Galletti, Bruno, Nuti, Sandra, De Gregorio, Ennio, Bertholet, Sylvie, Seubert, Anja, Bagnoli, Fabio, Bensi, Giuliano, Chiarot, Emiliano
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 30.11.2016; Nature Publishing Group
• Subjects: 13/31; 13/51; 14/19; 14/5; 631/250/255/1318; 631/326/590/2294; 64/60; Animals; Antibody response; Arthritis; Arthritis, Infectious - immunology; Arthritis, Infectious - microbiology; Arthritis, Infectious - pathology; Arthritis, Infectious - prevention & control; Bacteremia; Bacterial diseases; CD4 antigen; Effector cells; Female; Humanities and Social Sciences; Immune response; Immunization; Immunological memory; Inflammation; Joint diseases; Knee; Knee Joint - immunology; Knee Joint - microbiology; Knee Joint - pathology; Lymphocytes T; Memory cells; Mice; multidisciplinary; Osteomyelitis; Science; Staphylococcal Infections - immunology; Staphylococcal Infections - pathology; Staphylococcal Infections - prevention & control; Staphylococcal Vaccines - immunology; Staphylococcal Vaccines - pharmacology; Staphylococcus aureus - immunology; Toxicity; Vaccination; Vaccines
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep38043

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.