Investigation ofTrypanosoma-induced vascular damage sheds insights intoTrypanosoma vivaxsequestration

Abstract

AbstractMultiple blood-borne pathogens infecting mammals establish close interactions with the host vascular endothelium as part of their life cycles. In this work, we investigate differences in the interactions of threeTrypanosomaspecies:T. brucei, T. congolenseandT. vivaxwith the blood vasculature. Infection with these species results in vastly different pathologies, including different effects on vascular homeostasis, such as changes in vascular permeability and microhemorrhages. While all three species are extracellular parasites,T. congolenseis strictly intravascular, whileT. bruceiis capable of surviving both extra- and intravascularly. Our knowledge regardingT. vivaxtropism and its capacity of migration across the vascular endothelium is unknown. In this work, we show for the first time thatT. vivaxparasites sequester to the vascular endothelium of most organs, and that, likeT. congolense, T. vivaxY486 is largely incapable of extravasation. Infection with this parasite species results in a unique effect on vascular endothelium receptors including general downregulation of ICAM1 and ESAM, and upregulation of VCAM1, CD36 and E-selectin. Our findings on the differences between the two sequestering species (T. congolenseandT. vivax) and the non-sequestering, but extravasating,T. bruceiraise important questions on the relevance of sequestration to the parasite’s survival in the mammalian host, and the evolutionary relevance of both sequestration and extravasation.