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Experimental pneumococcal meningitis in mice: a model of intranasal infection
P J Zwijnenburg1, T van der Poll, S Florquin
1Department of Pediatrics, University Hospital Vrije Universiteit, and Department of Experimental Internal Medicine, Academic Medical Center, University of Amsterdam, 1105 AZ, Amsterdam, The Netherlands. p.j.zwijnenburg@amc.uva.nl
Abstract:
Effective laboratory animal models of bacterial meningitis are needed to unravel the pathophysiology of this disease. Previous models have failed to simulate human meningitis by using a directly intracerebral route of infection. Hyaluronidase is a virulence factor of Streptococcus pneumoniae. In this study, a novel model of murine meningitis is described. Intranasal administration of S. pneumoniae with hyaluronidase induced meningitis in 50% of inoculated mice, as defined by a positive cerebrospinal fluid (CSF) culture and an inflammatory infiltrate in the meninges. None of the mice inoculated without hyaluronidase developed meningitis. Hyaluronidase was found to facilitate pneumococcal invasion of the bloodstream after colonization of the upper respiratory tract. Meningitis was characterized by pleocytosis of CSF and the induction of proinflammatory cytokines and CXC chemokines in brain tissue. These results indicate that this murine model mimics important features of human disease and allow for the use of this model for studying issues related to the pathophysiology and the treatment of pneumococcal meningitis.
Insights
A new mouse model for bacterial meningitis uses Streptococcus pneumoniae with hyaluronidase, successfully mimicking human disease features. This model aids in studying meningitis pathophysiology and treatment strategies.
Area of Science:
- Microbiology
- Pathology
- Immunology
Background:
- Bacterial meningitis requires effective laboratory animal models for research.
- Existing models often fail to replicate human meningitis due to direct intracerebral infection routes.
- Streptococcus pneumoniae hyaluronidase is a key virulence factor.
Purpose of the Study:
- To develop and validate a novel murine model of bacterial meningitis.
- To investigate the role of hyaluronidase in Streptococcus pneumoniae meningitis.
- To establish a model that accurately simulates human meningitis pathophysiology.
Main Methods:
- Intranasal administration of Streptococcus pneumoniae with and without hyaluronidase in mice.
- Cerebrospinal fluid (CSF) culture to confirm infection.
- Histopathological examination of meninges for inflammatory infiltrate.
- Measurement of proinflammatory cytokines and chemokines in brain tissue.
Main Results:
- Intranasal inoculation with S. pneumoniae and hyaluronidase induced meningitis in 50% of mice.
- Meningitis was characterized by positive CSF cultures and meningeal inflammation.
- Mice inoculated without hyaluronidase did not develop meningitis.
- Hyaluronidase facilitated pneumococcal bloodstream invasion after upper respiratory tract colonization.
- CSF showed pleocytosis, and brain tissue exhibited elevated proinflammatory cytokines and chemokines.
Conclusions:
- The novel murine model effectively replicates key features of human bacterial meningitis.
- Hyaluronidase is crucial for inducing meningitis in this model by promoting bacterial invasion.
- This model provides a valuable tool for studying pneumococcal meningitis pathophysiology and therapeutic interventions.