Excreted Trypanosoma brucei proteins inhibit Plasmodium hepatic infection

Adriana Temporão, Margarida Sanches-Vaz, Rafael Luís, Helena Nunes-Cabaço, Terry K. Smith, Miguel Prudêncio*, Luisa M. Figueiredo*

*Corresponding author for this work

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Abstract

Malaria, a disease caused by Plasmodium parasites, remains a major threat to public health globally. It is the most common disease in patients with sleeping sickness, another parasitic illness, caused by Trypanosoma brucei. We have previously shown that a T. brucei infection impairs a secondary P. berghei liver infection and decreases malaria severity in mice. However, whether this effect requires an active trypanosome infection remained unknown. Here, we show that Plasmodium liver infection can also be inhibited by the serum of a mouse previously infected by T. brucei and by total protein lysates of this kinetoplastid. Biochemical characterisation showed that the anti-Plasmodium activity of the total T. brucei lysates depends on its protein fraction, but is independent of the abundant variant surface glycoprotein. Finally, we found that the protein(s) responsible for the inhibition of Plasmodium infection is/are present within a fraction of ~350 proteins that are excreted to the bloodstream of the host. We conclude that the defence mechanism developed by trypanosomes against Plasmodium relies on protein excretion. This study opens the door to the identification of novel antiplasmodial intervention strategies.
Original languageEnglish
Article numbere0009912
Number of pages28
JournalPLoS Neglected Tropical Diseases
Volume15
Issue number10
DOIs
Publication statusPublished - 29 Oct 2021

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