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Inducing Meningococcal Meningitis Serogroup C in Mice via Intracisternal Delivery
Published on: November 5, 2019
Inducing Meningococcal Meningitis Serogroup C in Mice via Intracisternal Delivery
Chiara Pagliuca1, Elena Scaglione1, Francesca Carraturo1
1Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II.
Abstract:
Neisseria meningitidis (meningococcus) is a narrow-host-range microorganism, globally recognized as the leading cause of bacterial meningitis. Meningococcus is a transient colonizer of human nasopharynx of approximately 10% of healthy subject. In particular circumstances, it acquires an invasive ability to penetrate the mucosal barrier and invades the bloodstream causing septicaemia. In the latest case, fulminating sepsis could arise even without the consequent development of meningitis. Conversely, bacteria could poorly multiply in the bloodstream, cross the blood brain barrier, reach the central nervous system, leading to fulminant meningitis. The murine models of bacterial meningitis represent a useful tool to investigate the host-pathogen interactions and to analyze the pathogenetic mechanisms responsible for this lethal disease. Although, several experimental model systems have been evaluated over the last decades, none of these were able to reproduce the characteristic pathological events of meningococcal disease. In this experimental protocol, we describe a detailed procedure for the induction of meningococcal meningitis in a mouse model based on the intracisternal inoculation of bacteria. The peculiar signs of human meningitis were recorded in the murine host through the assessment of clinical parameters (e.g., temperature, body weight), evaluation of survival rate, microbiological analysis and histological examination of brain injury. When using intracisternal (i.cist.) inoculum, meningococci complete delivery directly into cisterna magna, leading to a very efficient meningococcal replication in the brain tissue. A 1,000-fold increase of viable count of bacteria is observed in about 18 h. Moreover, meningococci are also found in the spleen, and liver of infected mice, suggesting that the liver may represent a target organ for meningococcal replication.
Insights
This study introduces a new mouse model for bacterial meningitis caused by Neisseria meningitidis (meningococcus). Intracisternal inoculation effectively replicates human meningitis signs, aiding research into this lethal infection.
Area of Science:
- Microbiology
- Pathogenesis
- Infectious Diseases
Background:
- Neisseria meningitidis (meningococcus) is a primary cause of bacterial meningitis and sepsis.
- Existing mouse models fail to fully replicate meningococcal disease pathology.
- Understanding host-pathogen interactions is crucial for developing effective treatments.
Purpose of the Study:
- To establish a reliable mouse model for studying meningococcal meningitis.
- To investigate the pathogenesis of Neisseria meningitidis infection.
- To analyze host-pathogen interactions during invasive meningococcal disease.
Main Methods:
- Developed a mouse model using intracisternal inoculation of Neisseria meningitidis.
- Monitored clinical parameters including temperature, body weight, and survival rates.
- Conducted microbiological and histological analyses of brain, spleen, and liver tissues.
Main Results:
- Intracisternal inoculation led to efficient meningococcal replication in brain tissue within 18 hours.
- The model reproduced key clinical signs observed in human meningitis.
- Neisseria meningitidis was detected in the spleen and liver, indicating systemic spread and potential target organ involvement.
Conclusions:
- The intracisternal inoculation mouse model effectively mimics human meningococcal meningitis.
- This model facilitates detailed investigation of meningococcal pathogenesis and host responses.
- The findings highlight the liver as a potential target organ in meningococcal infections.

