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An essential role for tumor necrosis factor in the formation of experimental murine Staphylococcus aureus-induced brain abscess and clearance
journal contributionposted on 2023-05-17, 07:46 authored by Stenzel, W, Soltek, S, Miletic, H, Hermann, MM, Heinrich KornerHeinrich Korner, Sedgwick, JD, Schluter, D, Deckert, M
Tumor necrosis factor-Î± (TNF-Î±) 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 (TNF0/0) mice were stereotaxically infected with Staphylococcus (S.) aureus-laden agarose beads. In comparison to 100% survival of wild type (WT) mice, TNF0/0 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 TNF0/0 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 TNF0/0 mice. Similarly, numbers of inflammatory leukocytes, cytokine expression of IL-6, IL-12p40, IFNÎ³, IL-1Î² mRNA, and brain edema were significantly increased in TNF0/0 mice as compared to WT animals. In addition, resolution of i.c. infiltrates was delayed in TNF0/0 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.
Publication titleJournal of Neuropathology and Experimental Neurology
Department/SchoolMenzies Institute for Medical Research
PublisherAmer Assn Neuropathologists Inc
Place of publication1041 New Hampshire St, Lawrence, USA, Ks, 66044