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Published on: January 17, 2014
Protein expression pattern in experimental pneumococcal meningitis
Matthias Klein1, Robert Paul, Barbara Angele
1Department of Neurology, Klinikum Grosshadern, Ludwig-Maximilian University, Marchioninistrasse 15, 81377 Munich, Germany.
Abstract:
In this study, we investigated cytokine expression during experimental pneumococcal meningitis. Mice were intracisternally infected with Streptococcus pneumoniae and treated with ceftriaxone starting at 24 h after infection. At different time points before and after antibiotic therapy, the cytokine expression pattern was determined in mouse brains using protein arrays. Underlining the power of this method, the meningitis-relevant cytokines interleukin-1beta (IL-1beta), IL-6, KC, macrophage inflammatory protein-2 (MIP-2), and monocyte chemoattractant protein-1 (MCP-1/CCL2) were markedly elevated in infected animals. Newly identified proteins during the acute stage of the disease (until 30 h after infection) included lymphotactin (XCL-1), MIP-1gamma (CCL9) and MCP-5 (CCL12), cytokine responsive gene- 2 (CRG-2/CXCL10) and CXCL16, and insulin-like growth factor binding protein 3 (IGFBP3). During later stages, an induction of T-cell activation-3 (TCA-3/CCL1), platelet factor-4 (PF-4/CXCL4) and stromal derived factor-1alpha (SDF-1alpha/CXCL13), and IL-4 was observed. The validity of this method was supported by an additional ELISA analysis of the expression profile of CXCL16 and IGFBP3, which was identical to that observed by protein array. In conclusion, the use of protein array technology led to an extension of the current picture of protein expression in pneumococcal meningitis. Most important, new factors that might play a role in pneumococcal meningitis were identified.
Insights
This study reveals novel protein expressions in experimental pneumococcal meningitis using protein arrays. New factors identified may play crucial roles in disease progression and treatment strategies.
Area of Science:
- Neuroscience
- Immunology
- Microbiology
Background:
- Pneumococcal meningitis is a severe infection with significant neurological consequences.
- Understanding the host's inflammatory response is crucial for developing effective treatments.
Purpose of the Study:
- To investigate cytokine and protein expression patterns in experimental pneumococcal meningitis.
- To identify novel proteins involved in the acute and later stages of the disease.
Main Methods:
- Intracisternal infection of mice with Streptococcus pneumoniae.
- Ceftriaxone treatment initiated 24 hours post-infection.
- Protein array analysis of mouse brain tissue at various time points.
- ELISA validation for selected proteins (CXCL16, IGFBP3).
Main Results:
- Marked elevation of known meningitis-relevant cytokines (IL-1beta, IL-6, KC, MIP-2, MCP-1/CCL2) in infected mice.
- Identification of novel proteins during acute infection: XCL-1, CCL9, CCL12, CXCL10, CXCL16, IGFBP3.
- Upregulation of T-cell related proteins (CCL1, CXCL4, CXCL13) and IL-4 during later stages.
- ELISA confirmed protein array findings for CXCL16 and IGFBP3.
Conclusions:
- Protein array technology significantly expands the understanding of protein expression in pneumococcal meningitis.
- Several newly identified proteins may represent novel therapeutic targets or biomarkers for pneumococcal meningitis.
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