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Q586B2 is a crucial virulence factor during the early stages of Trypanosoma brucei infection that is conserved amongst trypanosomatids

Author

Listed:
  • Benoit Stijlemans

    (Vrije Universiteit Brussel
    VIB Center for Inflammation Research)

  • Patrick Baetselier

    (Vrije Universiteit Brussel
    VIB Center for Inflammation Research)

  • Inge Molle

    (Vrije Universiteit Brussel
    VIB-VUB Center for Structural Biology)

  • Laurence Lecordier

    (Université Libre de Bruxelles)

  • Erika Hendrickx

    (IBMM, Université Libre de Bruxelles)

  • Ema Romão

    (Vrije Universiteit Brussel)

  • Cécile Vincke

    (Vrije Universiteit Brussel
    VIB Center for Inflammation Research)

  • Wendy Baetens

    (Vrije Universiteit Brussel
    VIB Center for Inflammation Research)

  • Steve Schoonooghe

    (Vrije Universiteit Brussel)

  • Gholamreza Hassanzadeh-Ghassabeh

    (Vrije Universiteit Brussel)

  • Hannelie Korf

    (KU Leuven)

  • Marie Wallays

    (KU Leuven)

  • Joar E. Pinto Torres

    (Vrije Universiteit Brussel)

  • David Perez-Morga

    (IBMM, Université Libre de Bruxelles
    Université Libre de Bruxelles)

  • Lea Brys

    (Vrije Universiteit Brussel
    VIB Center for Inflammation Research)

  • Oscar Campetella

    (Universidad Nacional de San Martín-CONICET)

  • María S. Leguizamón

    (Universidad Nacional de San Martín-CONICET)

  • Mathieu Claes

    (University of Antwerp)

  • Sarah Hendrickx

    (University of Antwerp)

  • Dorien Mabille

    (University of Antwerp)

  • Guy Caljon

    (University of Antwerp)

  • Han Remaut

    (Vrije Universiteit Brussel
    VIB-VUB Center for Structural Biology)

  • Kim Roelants

    (Vrije Universiteit Brussel)

  • Stefan Magez

    (Vrije Universiteit Brussel
    Ghent University Global Campus)

  • Jo A. Ginderachter

    (Vrije Universiteit Brussel
    VIB Center for Inflammation Research)

  • Carl Trez

    (Vrije Universiteit Brussel)

Abstract

Human African trypanosomiasis or sleeping sickness, caused by the protozoan parasite Trypanosoma brucei, is characterized by the manipulation of the host’s immune response to ensure parasite invasion and persistence. Uncovering key molecules that support parasite establishment is a prerequisite to interfere with this process. We identified Q586B2 as a T. brucei protein that induces IL-10 in myeloid cells, which promotes parasite infection invasiveness. Q586B2 is expressed during all T. brucei life stages and is conserved in all Trypanosomatidae. Deleting the Q586B2-encoding Tb927.6.4140 gene in T. brucei results in a decreased peak parasitemia and prolonged survival, without affecting parasite fitness in vitro, yet promoting short stumpy differentiation in vivo. Accordingly, neutralization of Q586B2 with newly generated nanobodies could hamper myeloid-derived IL-10 production and reduce parasitemia. In addition, immunization with Q586B2 delays mortality upon a challenge with various trypanosomes, including Trypanosoma cruzi. Collectively, we uncovered a conserved protein playing an important regulatory role in Trypanosomatid infection establishment.

Suggested Citation

  • Benoit Stijlemans & Patrick Baetselier & Inge Molle & Laurence Lecordier & Erika Hendrickx & Ema Romão & Cécile Vincke & Wendy Baetens & Steve Schoonooghe & Gholamreza Hassanzadeh-Ghassabeh & Hannelie, 2024. "Q586B2 is a crucial virulence factor during the early stages of Trypanosoma brucei infection that is conserved amongst trypanosomatids," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46067-4
    DOI: 10.1038/s41467-024-46067-4
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    References listed on IDEAS

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    1. Andrew W. Senior & Richard Evans & John Jumper & James Kirkpatrick & Laurent Sifre & Tim Green & Chongli Qin & Augustin Žídek & Alexander W. R. Nelson & Alex Bridgland & Hugo Penedones & Stig Petersen, 2020. "Improved protein structure prediction using potentials from deep learning," Nature, Nature, vol. 577(7792), pages 706-710, January.
    2. Guillaume Hoeffel & Guilhaume Debroas & Anais Roger & Rafaelle Rossignol & Jordi Gouilly & Caroline Laprie & Lionel Chasson & Pierre-Vincent Barbon & Anaïs Balsamo & Ana Reynders & Aziz Moqrich & Soph, 2021. "Sensory neuron-derived TAFA4 promotes macrophage tissue repair functions," Nature, Nature, vol. 594(7861), pages 94-99, June.
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