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Inducing Meningococcal Meningitis Serogroup C in Mice via Intracisternal Delivery
Published on: November 5, 2019
Evidence for Multi-Organ Infection During Experimental Meningococcal Sepsis due to ST-11 Isolates in Human
Michael Levy1,2,3, Myriam Aouiti Trabelsi1, Muhamed-Kheir Taha1
1Institut Pasteur, Invasive Bacterial Infection Unit, 28 rue du Dr Roux, 75724 Paris, France.
Abstract:
The description of invasive meningococcal disease that is provoked by Neisseria meningitidis (Nm) is frequently restricted to meningitis. However, a wide panel of clinical presentations can be encountered including severe forms with intense inflammatory reaction leading to multi-organ failure. Several human factors are involved in the development of invasive infections such as transferrin, factor H or CEACAM1. In this study, we used an experimental meningococcal infection in transgenic mice expressing the human transferrin to show multi-organ infection. Mice were infected by an intraperitoneal injection of bacterial suspension (1.5 × 107 colony-forming unit/mouse) of a bioluminescent serogroup C strain belonging to the clonal complex ST-11. Dynamic imaging and histological analysis were performed. The results showed invasion of tissues by Nm with bacteria observed, outside blood vessels, in the kidneys, the heart and the brain as well as skin involvement. These data further support the systemic aspect of invasive meningococcal disease with involvement of several organs including skin as in humans. Thus, our model can be used to study severe forms of meningococcal invasive infections with multi-organ failure.
Insights
Invasive meningococcal disease extends beyond meningitis, affecting multiple organs. This study demonstrates Neisseria meningitidis (Nm) infection in kidneys, heart, brain, and skin using a novel mouse model.
Area of Science:
- Microbiology and Immunology
- Infectious Diseases
- Pathogenesis Research
Background:
- Invasive meningococcal disease (IMD) caused by Neisseria meningitidis (Nm) is often limited to meningitis descriptions.
- Severe IMD can manifest with multi-organ failure due to intense inflammatory responses.
- Human factors like transferrin influence invasive infection development.
Purpose of the Study:
- To investigate the systemic spread and multi-organ involvement in experimental invasive meningococcal disease.
- To utilize a transgenic mouse model expressing human transferrin for studying Nm infection.
- To explore the potential of this model for severe IMD research, including multi-organ failure.
Main Methods:
- Infection of transgenic mice expressing human transferrin with a bioluminescent Neisseria meningitidis serogroup C strain (ST-11).
- Intraperitoneal injection of bacterial suspension (1.5 × 10^7 CFU/mouse).
- Dynamic imaging and histological analysis to track bacterial dissemination and tissue invasion.
Main Results:
- Demonstrated multi-organ invasion by Neisseria meningitidis in the experimental model.
- Observed bacterial presence outside blood vessels in kidneys, heart, brain, and skin.
- Confirmed systemic dissemination consistent with human invasive meningococcal disease presentations.
Conclusions:
- Invasive meningococcal disease is a systemic infection involving multiple organs, including the skin.
- The developed mouse model effectively replicates human IMD, showing multi-organ involvement.
- This model is suitable for studying severe forms of invasive meningococcal disease and associated multi-organ failure.

