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Updated: Oct 26, 2025

Humanized Mouse Model to Study Bacterial Infections Targeting the Microvasculature
Published on: April 1, 2014
Colonization of dermal arterioles by Neisseria meningitidis provides a safe haven from neutrophils
Valeria Manriquez1, Pierre Nivoit1, Tomas Urbina1
1Pathogenesis of Vascular Infections unit, INSERM, Institut Pasteur, Paris, France.
Abstract:
The human pathogen Neisseria meningitidis can cause meningitis and fatal systemic disease. The bacteria colonize blood vessels and rapidly cause vascular damage, despite a neutrophil-rich inflammatory infiltrate. Here, we use a humanized mouse model to show that vascular colonization leads to the recruitment of neutrophils, which partially reduce bacterial burden and vascular damage. This partial effect is due to the ability of bacteria to colonize capillaries, venules and arterioles, as observed in human samples. In venules, potent neutrophil recruitment allows efficient bacterial phagocytosis. In contrast, in infected capillaries and arterioles, adhesion molecules such as E-Selectin are not expressed on the endothelium, and intravascular neutrophil recruitment is minimal. Our results indicate that the colonization of capillaries and arterioles by N. meningitidis creates an intravascular niche that precludes the action of neutrophils, resulting in immune escape and progression of the infection.
Insights
Neisseria meningitidis evades immune responses by colonizing capillaries and arterioles, creating a niche that prevents neutrophils from attacking the bacteria, leading to disease progression.
Area of Science:
- Microbiology
- Immunology
- Pathogenesis
Background:
- Neisseria meningitidis is a human pathogen causing meningitis and fatal systemic disease.
- The bacteria rapidly damage vasculature despite neutrophil presence.
Purpose of the Study:
- To investigate how Neisseria meningitidis vascular colonization leads to immune evasion.
- To understand the role of neutrophils in controlling N. meningitidis infection in different vascular compartments.
Main Methods:
- Utilized a humanized mouse model to study N. meningitidis vascular colonization.
- Observed bacterial localization and neutrophil recruitment in capillaries, venules, and arterioles.
- Assessed expression of adhesion molecules like E-Selectin on the endothelium.
Main Results:
- Neutrophil recruitment partially reduced bacterial burden and vascular damage.
- N. meningitidis colonized capillaries, venules, and arterioles, consistent with human samples.
- Efficient neutrophil phagocytosis occurred in venules.
- Minimal neutrophil recruitment was observed in capillaries and arterioles due to lack of E-Selectin expression.
Conclusions:
- N. meningitidis establishes an immune-privileged niche in capillaries and arterioles.
- This niche allows bacteria to evade neutrophil action, promoting infection progression.
- Targeting these specific vascular niches may offer new therapeutic strategies.
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