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An essential role for tumor necrosis factor in the formation of experimental murine Staphylococcus aureus-induced brain abscess and clearance

Citation

Stenzel, W and Soltek, S and Miletic, H and Hermann, MM and Korner, H and Sedgwick, JD and Schluter, D and Deckert, M, An essential role for tumor necrosis factor in the formation of experimental murine Staphylococcus aureus-induced brain abscess and clearance, Journal of Neuropathology and Experimental Neurology, 64, (1) pp. 27-36. ISSN 0022-3069 (2005) [Refereed Article]

DOI: doi:10.1093/jnen/64.1.27

Abstract

Tumor necrosis factor-α (TNF-α) 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, IFNγ, IL-1β 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.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Immunology
Research Field:Immunology not elsewhere classified
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Infectious Diseases
Author:Korner, H (Professor Heinrich Korner)
ID Code:72495
Year Published:2005
Web of Science® Times Cited:26
Deposited By:Research Division
Deposited On:2011-08-29
Last Modified:2011-11-08
Downloads:0

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