Immunopathology and Trypanosoma congolense parasite sequestration cause acute cerebral trypanosomiasis
- Universidade de Lisboa, Portugal
Abstract
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 hours) 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.
Data availability
Sequencing reads are available from NCBI under BioProject accession number: PRJNA777781.
Article and author information
Author details
Sara Silva Pereira
Funding
European Research Council (771714,679368)
- Cláudio A Franco
- Luisa Figueiredo
Human Frontier Science Program (LT000047/2019-L)
- Mariana De Niz
European Molecular Biology Organization (ALTF 1048-2016)
- Mariana De Niz
HORIZON EUROPE Marie Sklodowska-Curie Actions (839960)
- Sara Silva Pereira
Fundaçäo para a Ciéncia e a Tecnologia (CEECIND/03322/2018,CEECIND/00697/2018,CEECIND/04251/2017)
- Karine Serre
- Cláudio A Franco
- Luisa Figueiredo
Fondation Leducq (17CVD03)
- Cláudio A Franco
Fundaçäo para a Ciéncia e a Tecnologia (IF/00412/2012,EXPL/BEX-BCM/2258/2013,PRECISE-LISBOA-01-0145-FEDER-016394,PTDC/MED-PAT/31639/2017)
- Cláudio A Franco
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was conducted in accordance with EU regulations and ethical approval was obtained from the Animal Ethics Committee of Instituto de Medicina Molecular (AWB_2016_07_LF_Tropism). All surgeries were performed under anaesthesia, and every effort was made to minimize suffering.
Copyright
© 2022, Silva Pereira et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Immunopathology and Trypanosoma congolense parasite sequestration cause acute cerebral trypanosomiasis
eLife 11:e77440.
https://doi.org/10.7554/eLife.77440
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