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Central nervous system TNFalpha-mRNA expression during rabbit experimental pneumococcal meningitis
A Bitsch1, F Trostdorf, W Brück
1Department of Neurology, University of Göttingen, Germany. abitsch@t-online.de
Abstract:
In pneumococcal meningitis inflammatory mediators such as tumor necrosis factor alpha (TNFalpha) are produced in large quantities and play a major role in pathogenesis. It is not known exactly which cells produce these mediators during infection. We investigated the localisation of TNFalpha-mRNA in the central nervous system (CNS) by in situ hybridisation during experimental Streptococcus pneumoniae meningitis. TNF-positive cells were detected only in inflammatory infiltrates within the meninges. Cells within the brain parenchyma and the choroid plexus were completely negative. After monocyte depletion, no TNFalpha-mRNA positive cells were detected in the CNS. These findings suggest that TNFalpha in pneumococcal meningitis is produced in the CNS mainly by blood-derived, infiltrating monocytes.
Insights
In pneumococcal meningitis, tumor necrosis factor alpha (TNFalpha) is mainly produced by infiltrating monocytes in the central nervous system (CNS). This finding clarifies the cellular source of key inflammatory mediators during this infection.
Area of Science:
- Neuroimmunology
- Infectious Diseases
- Pathogenesis Research
Background:
- Pneumococcal meningitis involves significant inflammation driven by mediators like tumor necrosis factor alpha (TNFalpha).
- The precise cellular origin of TNFalpha within the central nervous system (CNS) during infection remains unclear.
Purpose of the Study:
- To investigate the cellular localization of TNFalpha-mRNA in the CNS during experimental Streptococcus pneumoniae meningitis.
- To identify the specific cell types responsible for TNFalpha production in the context of pneumococcal meningitis.
Main Methods:
- In situ hybridization was employed to detect TNFalpha-mRNA.
- Experiments involved an animal model of Streptococcus pneumoniae meningitis.
- Monocyte depletion was utilized as a method to assess cellular contribution.
Main Results:
- TNFalpha-mRNA positive cells were exclusively found within inflammatory infiltrates in the meninges.
- No TNFalpha-mRNA positive cells were observed in the brain parenchyma or choroid plexus.
- Depletion of monocytes resulted in the complete absence of TNFalpha-mRNA positive cells in the CNS.
Conclusions:
- In pneumococcal meningitis, TNFalpha production within the CNS is primarily attributed to blood-derived monocytes infiltrating the meninges.
- These findings highlight the critical role of infiltrating monocytes in the inflammatory response during pneumococcal meningitis.