An essential role for tumor necrosis factor in the formation of experimental murine Staphylococcus aureus-induced brain abscess and clearance.
Tumor necrosis factor-alpha (TNF-alpha) is a central mediator of the immune response to pathogens, but may also exert neurotoxic effects, thereby contributing to immunopathology. To define the role of TNF during the course of brain abscess, TNF-deficient (TNF(0/0) mice were stereotaxically infected with Staphylococcus (S.) aureus-laden agarose beads. In comparison to 100% survival of wild type (WT) mice, TNF(0/0) mice displayed high mortality rates (54%) in the initial phase of abscess development as well as significantly increased morbidity in the course of the disease. The worse clinical outcome was due to an increased intracerebral (i.c.) bacterial load in TNF(0/0) mice as compared to WT mice. The impaired control of S. aureus was associated with reduced inductible nitric oxide synthase (iNOS) mRNA and protein expression in TNF(0/0)mice. Similarly, numbers of inflammatory leukocytes, cytokine expression of IL-6, IL-12p40, IFNgamma IL-beta mRNA, and brain edema were significantly increased in TNF(0/0)mice as compared to WT animals. In addition, resolution of i.c. infiltrates was delayed in TNF(0/0)mice correlating with reduced apoptosis of inflammatory leukocytes and formation of a fibrous abscess capsule. Collectively, these data demonstrate that TNF is of key importance for the control of S. aureus-induced brain abscess and regulates the ensuing host immune response.
Stenzel
Werner
W
Abteilung für Neuropathologie, Universität zu Köln, Germany.
Soltek
Sabine
S
Miletic
Hrvoje
H
Hermann
Manuel Marcel
MM
Körner
Heinrich
H
Sedgwick
Jonathon D
JD
Schlüter
Dirk
D
Deckert
Martina
M
D000818:Animals; D001922:Brain Abscess / Q000235:genetics / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis; D007962:Leukocytes / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013203:Staphylococcal Infections / Q000235:genetics / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D013211:Staphylococcus aureus / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha