Abstract: © 2022, Silva Pereira, De Niz et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited. ; Trypanosoma congolense causes a syndrome of variable severity in animals in Africa. Cerebral trypanosomiasis is a severe form, but the mechanism underlying this severity remains unknown. We developed a mouse model of acute cerebral trypanosomiasis and characterized the cellular, behavioral, and physiological consequences of this infection. We show large parasite sequestration in the brain vasculature for long periods of time (up to 8 hr) and extensive neuropathology that associate with ICAM1-mediated recruitment and accumulation of T cells in the brain parenchyma. Antibody-mediated ICAM1 blocking and lymphocyte absence reduce parasite sequestration in the brain and prevent the onset of cerebral trypanosomiasis. Here, we establish a mouse model of acute cerebral trypanosomiasis and we propose a mechanism whereby parasite sequestration, host ICAM1, and CD4+ T cells play a pivotal role. ; This work was supported by European Union’s Horizon 2020 research and innovation program through a Marie Skłodowska-Curie Individual Standard European Fellowship to S.S.P., under grant agreement no. 839960, and from the European Research Council (ERC) (FatTryp, 771714) to L.M.F. M.D.N. was funded by Human Frontiers LT000047/2019 L (HFSP) and EMBO (ALTF 1048–2016). L.M.F., K.S., and C.A.F. are Investigators CEEC of the Fundação para a Ciência e a Tecnologia (CEECIND/03322/2018, CEECIND/00697/2018, CEECIND/04251/2017, respectively). C.A.F. was supported by a European Research Council starting grant (679368), the Fondation Leducq (17CVD03), and the Fundação para a Ciência e a Tecnologia (grants IF/00412/2012, EXPL/BEX- BCM/2258/2013, PRECISE-LISBOA-01–0145-FEDER-016394, PTDC/MED-PAT/31639/2017, PTDC/BIA-CEL/32180/2017). ; info:eu-repo/semantics/publishedVersion
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