Immunopathology and Trypanosoma congolense parasite sequestration cause acute cerebral trypanosomiasis

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.

The following data sets were generated

Article and author information

Author details

  1. Sara Silva Pereira

    Instituto de Medicina Molecular, Universidade de Lisboa, Lisbon, Portugal
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6590-6626
  2. Mariana De Niz

    Instituto de Medicina Molecular, Universidade de Lisboa, Lisbon, Portugal
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6987-6789
  3. Karine Serre

    Instituto de Medicina Molecular, Universidade de Lisboa, Lisbon, Portugal
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9152-4739
  4. Marie Ouarné

    Instituto de Medicina Molecular, Universidade de Lisboa, Lisbon, Portugal
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4724-4363
  5. Joana E Coelho

    Instituto de Medicina Molecular, Universidade de Lisboa, Lisbon, Portugal
    Competing interests
    The authors declare that no competing interests exist.
  6. Cláudio A Franco

    Instituto de Medicina Molecular, Universidade de Lisboa, Lisbon, Portugal
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2861-3883
  7. Luisa Figueiredo

    Instituto de Medicina Molecular, Universidade de Lisboa, Lisbon, Portugal
    For correspondence
    lmf@medicina.ulisboa.pt
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5752-6586

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.

Reviewing Editor

  1. Olivier Silvie, Sorbonne Université, UPMC Univ Paris 06, INSERM, CNRS, France

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.

Version history

  1. Preprint posted: November 5, 2021 (view preprint)
  2. Received: January 28, 2022
  3. Accepted: July 4, 2022
  4. Accepted Manuscript published: July 5, 2022 (version 1)
  5. Version of Record published: July 18, 2022 (version 2)

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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  1. Sara Silva Pereira
  2. Mariana De Niz
  3. Karine Serre
  4. Marie Ouarné
  5. Joana E Coelho
  6. Cláudio A Franco
  7. Luisa Figueiredo
(2022)
Immunopathology and Trypanosoma congolense parasite sequestration cause acute cerebral trypanosomiasis
eLife 11:e77440.
https://doi.org/10.7554/eLife.77440

Share this article

https://doi.org/10.7554/eLife.77440

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