Immunopathology and parasite sequestration cause severe cerebral trypanosomiasis in animals

Trypanosoma congolense causes a syndrome of variable severity in animals in sub-Saharan Africa.Cerebral trypanosomiasis is an acute form, but the mechanism underlying this severity remains unknown. We developed a mouse model of cerebral trypanosomiasis with T. congolense strain 1/148 and characterized the cellular, behavioral and physiological consequences of this infection. Using invivo imaging, we show large parasite sequestration in the brain vasculature for long periods of time (upto 8 hours), that results in extensive brain damage partly caused by ICAM1 - mediated recruitment and accumulation of T cells. Antibody-mediated ICAM1 blocking and lymphocyte absence reduce parasite sequestration in the brain and prevent the onset of cerebral trypanosomiasis. Here, we establish a new mouse model of cerebral trypanosomiasis and we propose a mechanism whereby parasite sequestration,host ICAM1, and T cells play a pivotal role.