Immunopathology and parasite sequestration cause severe cerebral trypanosomiasis in animals

Abstract

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 in vivo imaging, we show large parasite sequestration in the brain vasculature for long periods of time (up to 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.