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Updated: Aug 8, 2026
Humanized Mouse Model to Study Bacterial Infections Targeting the Microvasculature
Published on: April 1, 2014
Experimental meningococcal infection in mice: a model for mucosal invasion
Abstract:
A more complete understanding of meningococcal disease has been hampered by the lack of an appropriate animal model. Previous models have utilized injections of meningococci, which precludes the study of nasopharyngeal colonization and invasion. We have developed a model for meningococcal disease in which litters of 5-day-old mice are challenged intranasally with 10(7) viable meningococci. Bacteremia is monitored by jugular venous blood cultures, and cerebrospinal fluid is sampled by cisternal punctures. Human disease-associated and carrier strains were compared; nasopharyngeal colonization was similar for these bacteria, but the case-associated strains were much more frequently invasive and caused bacteremia. Twenty-one percent of bacteremic animals had meningitis. There was an age-related susceptibility to infection which correlated inversely with the levels of serum complement. Preinjection of iron dextran increased the number of animals which were bacteremic, the concentration of bacteria in blood, and nasopharyngeal colonization. Noncapsular variants of virulent meningococci did not colonize nasopharyngeal tissue in vivo, and they were not invasive. This neonatal mouse model mimics meningococcal disease as seen in humans and may be useful in studying the initial events in the pathogenesis of meningococcal disease.
Insights
Researchers developed a new neonatal mouse model for meningococcal disease. This model allows studying nasopharyngeal colonization and invasion, crucial for understanding disease pathogenesis.
Area of Science:
- Microbiology
- Infectious Diseases
- Animal Models
Background:
- Understanding meningococcal disease pathogenesis is limited by the lack of suitable animal models.
- Previous models using direct injections of meningococci do not allow for studying key aspects like nasopharyngeal colonization and invasion.
Purpose of the Study:
- To develop and validate a novel neonatal mouse model for studying meningococcal disease.
- To compare the invasiveness of human disease-associated and carrier strains of meningococci in vivo.
- To investigate factors influencing meningococcal infection, including age, complement levels, iron dextran, and bacterial capsule presence.
Main Methods:
- Intranasal challenge of 5-day-old mice with viable meningococci.
- Monitoring bacteremia via jugular venous blood cultures and cerebrospinal fluid sampling.
- Comparison of disease-associated and carrier strains, and evaluation of noncapsular variants.
- Assessment of age-related susceptibility and the impact of iron dextran.
Main Results:
- Neonatal mice intranasally inoculated with meningococci developed bacteremia and, in 21% of cases, meningitis.
- Disease-associated strains were significantly more invasive than carrier strains, despite similar nasopharyngeal colonization.
- Age-related susceptibility to infection correlated inversely with serum complement levels.
- Iron dextran administration increased bacteremia, bacterial concentration, and colonization.
- Noncapsular variants failed to colonize and invade.
Conclusions:
- The developed neonatal mouse model effectively mimics human meningococcal disease, including nasopharyngeal colonization, invasion, bacteremia, and meningitis.
- This model provides a valuable tool for investigating the early pathogenic events of meningococcal infections.
- The findings highlight the importance of bacterial capsule and host complement in meningococcal disease pathogenesis.
