PhD ceremony Mr. F. Iovino: Streptococcus pneumoniae interactions with endothelial cells leading to invasive pneumococcal disease

PhD ceremony: Mr. F. Iovino, 16.15 uur, Academiegebouw, Broerstraat 5, Groningen

Dissertation: Streptococcus pneumoniae interactions with endothelial cells leading to invasive pneumococcal disease

Promotor(s): prof. J.M. van Dijl, prof. G. Molema

Faculty: Medical Sciences

Meningitis is a serious invasive disease causing considerable mortality and morbidity worldwide. How bacterial pathogens cross the blood brain barrier and enter the CNS is currently unclear. Receptor-mediated adhesion of the bacteria to the brain endothelium is considered a key event leading to meningitis development. Streptococcus pneumoniae (the pneumococcus) is the main causative agent of bacterial meningitis in Europe and in the USA and is thought to invade the brain via the bloodstream by crossing the vasculature of the blood-brain barrier (BBB). The aim of this PhD research was to elucidate the spatio-temporal interactions of blood-borne S. pneumoniae with the blood-brain barrier endothelium during the events leading up to meningitis, and to characterize the receptors involved. The studies described in this thesis show that adhesion to the blood brain barrier is spatiotemporally controlled at different sites throughout the brain and that the local immune system is activated immediately upon entry of the bacteria into the bloodstream. They also provide evidence that pIgR, a well-known epithelial receptor for pneumococci, is also expressed by brain endothelial cells and may be a novel adhesin for the bacteria on the BBB. The research described in the last experimental chapter indicates that PECAM-1 could well be another novel receptor for S. pneumoniae on the BBB endothelium. Altogether, the research described in this thesis has provided novel insights in the adhesion of S. pneumoniae to the brain vascular endothelium, a crucial step in the passage of pneumococci across the BBB leading to meningitis.