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Title
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Q586B2 is a crucial virulence factor during the early stages of Trypanosoma brucei infection that is conserved amongst trypanosomatids
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Author
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Abstract
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| 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. |
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Language
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English
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Source (journal)
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Nature communications
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Publication
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2024
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ISSN
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2041-1723
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DOI
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10.1038/S41467-024-46067-4
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Volume/pages
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15
:1
(2024)
, p. 1-18
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Article Reference
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1779
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ISI
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001178774300022
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Pubmed ID
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38413606
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Full text (Publisher's DOI)
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Full text (open access)
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