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

Benoit Stijlemans, Patrick De Baetselier, Inge Van Molle, Laurence Lecordier, Erika Hendrickx, Ema Romão, Cécile Vincke, Wendy Baetens, Steve Schoonooghe, Gholamreza Hassanzadeh-Ghassabeh, Hannelie Korf, Marie Wallays, Joar E Pinto Torres, David Perez-Morga, Lea Brys, Oscar Campetella, María S Leguizamón, Mathieu Claes, Sarah Hendrickx, Dorien MabilleGuy Caljon, Han Remaut, Kim Roelants, Stefan Magez, Jo A Van Ginderachter, Carl De Trez

Onderzoeksoutput: Articlepeer review

Samenvatting

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.
Originele taal-2English
Artikelnummer1779
Aantal pagina's16
TijdschriftNature Communications
Volume15
Nummer van het tijdschrift1
DOI's
StatusPublished - 27 feb 2024

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© 2024. The Author(s).

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