title: Enhanced acute immune response in IL-12p35-/- mice is followed by accelerated distinct repair mechanisms in Staphylococcus aureus-induced murine brain abscess.
abstract: BACKGROUND
  Murine Staphylococcus aureus-mediated brain abscess comprises 2 major phases, an initial phase of cerebritis, followed by a healing phase characterized by capsule formation.
  
  
  METHODS
  C57BL/6 wild-type (WT) and IL-12p35(-/-) mice were intracerebrally infected with S. aureus to induce brain abscesses. Clinical disease activity and bacterial load were monitored. The cell populations that were involved, as well as their specific mediators, were analyzed by immunohistochemistry, quantitative real-time polymerase chain reaction, and flow cytometry.
  
  
  RESULTS
  In the acute phase, IL-12p35(-/-) mice were protected from disease. This was associated with enhanced recruitment of granulocytes, accompanied by upregulated expression of Il17a, Csf2 (which encodes granulocyte-macrophage colony-stimulating factor), Cxcl1, and Cxcl5, as well as increased expression of proinflammatory mediators, including Nos2 (which encodes inducible nitric oxide synthase), Ptgs2 (which encodes cyclooxygenase 2), and Tnf, that were primarily produced by granulocytes and activated microglia/macrophages. Furthermore, mechanisms associated with beneficial wound healing, including an accelerated formation of a fibrous capsule, were demonstrated by prominent VEGF-A production and collagen deposition driven by an earlier onset of T-helper 2 immunity in the absence of interleukin 12 (IL-12).
  
  
  CONCLUSIONS
  Brain abscess development is orchestrated by IL-12 at different stages of disease. Our data indicate that IL-12 has a nonprotective role in the acute phase and that IL-12 deficiency results in the accelerated formation of a protective capsule during the healing phase, which we consider crucial for early recovery from disease.
authors.affiliation: Department of Neuropathology, Charité-Universitätsmedizin Berlin, Germany.
authors.forename: Josephin
authors.initials: J
authors.lastname: Held
authors.forename: Corinna
authors.initials: C
authors.lastname: Preuße
authors.forename: Alexandra
authors.initials: A
authors.lastname: Döser
authors.forename: Lydia
authors.initials: L
authors.lastname: Richter
authors.forename: Frank L
authors.initials: FL
authors.lastname: Heppner
authors.forename: Werner
authors.initials: W
authors.lastname: Stenzel
mesh_terms: D000818:Animals; D058491:Bacterial Load; D001922:Brain Abscess / Q000276:immunology* / Q000382:microbiology / Q000473:pathology*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D053765:Interleukin-12 Subunit p35 / Q000172:deficiency*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D060888:Real-Time Polymerase Chain Reaction; D013203:Staphylococcal Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology*; D013211:Staphylococcus aureus / Q000276:immunology*
chemical_list: D053765:Interleukin-12 Subunit p35
keywords: IL-12; alternatively activated macrophages; brain abscess; capsule formation; chemokines; fibrosis; neoangiogenesis