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.
Highlights
Neisseria meningitidis (Nm) is a strict human pathogen that is frequently carried asymptomatically in the nasopharynx
Bacteria were grown on Gonococcal base (GCB) medium supplemented with Kellogg supplements
Experimental meningococcal infections were performed in 8 week-old female BALB/c transgenic mice expressing human transferrin [21] by intraperitoneal injection of 1.5 × 107 colony-forming unit (CFU)/mouse diluted in 0.5 mL of saline
Summary
Neisseria meningitidis (Nm) is a strict human pathogen that is frequently carried asymptomatically in the nasopharynx. Transgenic mouse models for meningococcal disease have been developed and used to study pathophysiological aspects of invasive meningococcal infections using intraperitoneal or intranasal experimental infection. These models used human CEACAM1 transgenic mice [8,9], human CD46 transgenic mice [10,11] and human complement factor H transgenic mice [12,13]. Transgenic mice expressing the human transferrin provide Nm with an appropriate human iron source; the human transferrin This model has been used to study several aspects of meningococcal virulence. We aimed in this work to address the multi-organ feature of IMD using transgenic mice expressing the human transferrin
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