title: The dynamics of T cells during persistent Staphylococcus aureus infection: from antigen-reactivity to in vivo anergy.
abstract: Staphylococcus aureus is an important human pathogen that can cause long-lasting persistent infections. The mechanisms by which persistent infections are maintained involve both bacterial escape strategies and modulation of the host immune response. So far, the investigations in this area have focused on strategies used by S. aureus to persist within the host. Here, we used an experimental mouse model to investigate the host response to persistent S. aureus infection. Our results demonstrated that T cells, which are critical for controlling S. aureus infection, gradually lost their ability to respond to antigenic stimulation and entered a state of anergy with the progression of infection towards persistence. The T cell hyporesponsiveness was reverted by co-stimulation with the phorbol ester PMA, an activator of protein kinase C, suggesting that a failure in the T cell receptor (TCR)-proximal signalling events underlie the hyporesponsive phenotype. The presence of these anergic antigen-specific T cells may contribute to the failure of the host immune response to promote sterilizing immunity during persistent S. aureus infection and also offers new possibilities for novel immunotherapeutic approaches.
authors: Infection Immunology Research Group, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors: Christina
authors: C
authors: Ziegler
authors: Oliver
authors: O
authors: Goldmann
authors: Elias
authors: E
authors: Hobeika
authors: Robert
authors: R
authors: Geffers
authors: Georg
authors: G
authors: Peters
authors: Eva
authors: E
authors: Medina
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D017635:Clonal Anergy; D005260:Female; D006801:Humans; D007668:Kidney / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013203:Staphylococcal Infections / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000276:immunology* / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D011948:Receptors, Antigen, T-Cell