Infection-on-Chip: anin vitrohuman vessel to studyNeisseria meningitidiscolonization and vascular damages

Abstract

AbstractBloodstream infections leading to sepsis are a life-threatening condition and remain difficult to treat, however,in vitroexperimental models that reflect their key features are still lacking. We here developed a photoablation-based 3-dimensional, microfluidic model of meningococcal vascular colonization, which allows to study cardinal features of the bacteria-blood vessel interaction within controllable vascular geometries. Meningococci are Gram-negative human-specific bacteria responsible for meningitis and a severe form of sepsis that is associated with vascular damages, referred to aspurpura fulminans. The infection-on-chip device is used to quantitatively assess bacterial adhesion and proliferation at high spatio-temporal resolution in a physiologically relevant microenvironment. In addition, we here show that vascular colonization by meningococci in our Infection-on-Chip device recapitulates key features of disease progression, including vascular leakage and the recruitment of neutrophils to sites of infections, mirroring results obtained using our previously described human skin xenograft mouse model. As a result, our Infection-on-chip platform provides a robust alternative approach to the use of animal and 2D cellular models, opening the path to the better understanding of disease progression and testing innovative therapeutics in anin vitrobut physiologically relevant environment.