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Updated: May 1, 2026
Humanized Mouse Model to Study Bacterial Infections Targeting the Microvasculature
Published on: April 1, 2014
Humanized mouse model to study bacterial infections targeting the microvasculature
Keira Melican1, Flore Aubey1, Guillaume Duménil2
1INSERM U970, Paris Cardiovascular Research Centre; Faculté de Médecine Paris Descartes, Université Paris Descartes.
Abstract:
Neisseria meningitidis causes a severe, frequently fatal sepsis when it enters the human blood stream. Infection leads to extensive damage of the blood vessels resulting in vascular leak, the development of purpuric rashes and eventual tissue necrosis. Studying the pathogenesis of this infection was previously limited by the human specificity of the bacteria, which makes in vivo models difficult. In this protocol, we describe a humanized model for this infection in which human skin, containing dermal microvessels, is grafted onto immunocompromised mice. These vessels anastomose with the mouse circulation while maintaining their human characteristics. Once introduced into this model, N. meningitidis adhere exclusively to the human vessels, resulting in extensive vascular damage, inflammation and in some cases the development of purpuric rash. This protocol describes the grafting, infection and evaluation steps of this model in the context of N. meningitidis infection. The technique may be applied to numerous human specific pathogens that infect the blood stream.
Insights
A novel humanized mouse model allows studying Neisseria meningitidis sepsis. This model uses human skin grafts to observe bacterial pathogenesis and vascular damage, aiding in developing new treatments.
Area of Science:
- Infectious Diseases
- Pathogenesis Research
- Animal Models
Background:
- Neisseria meningitidis causes life-threatening sepsis with severe vascular damage.
- Studying N. meningitidis pathogenesis is challenging due to its human specificity, limiting in vivo models.
- Existing models do not fully replicate human vascular responses to meningococcal infection.
Purpose of the Study:
- To develop and validate a humanized mouse model for studying Neisseria meningitidis pathogenesis.
- To investigate the mechanisms of vascular damage and purpuric rash development in meningococcal sepsis.
- To provide a platform for evaluating potential therapeutic interventions against human-specific pathogens.
Main Methods:
- Grafting human skin with dermal microvessels onto immunocompromised mice.
- Allowing vascular anastomosis between human graft and mouse circulation.
- Infecting the humanized model with Neisseria meningitidis and evaluating host-pathogen interactions.
Main Results:
- N. meningitidis selectively adhered to the human dermal microvessels within the graft.
- The model demonstrated extensive vascular damage, inflammation, and purpuric rash formation.
- Human vessels maintained their integrity and human characteristics post-anastomosis.
Conclusions:
- The humanized skin graft model effectively replicates key aspects of Neisseria meningitidis sepsis.
- This model provides a valuable tool for studying the pathogenesis of human-specific vascular infections.
- The technique is adaptable for investigating other blood-stream pathogens with human specificity.
