Figueiredo, Luísa MirandaPrudêncio, MiguelTemporão, Adriana2024-03-192024-03-192022-052022-01http://hdl.handle.net/10451/63563Malaria and sleeping sickness, infectious diseases caused by Plasmodium parasites and Trypanosoma brucei, respectively, share geographical space in sub-Saharan Africa. Malaria is not only a major threat to public health globally but also the most common infectious disease to occur in patients with sleeping sickness. The host labs 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 sought to assess whether an active T. brucei infection was required for this impairment, and to unravel the mechanism behind this phenomenon. We found 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 two life cycle stages of this kinetoplastid. Additionally, mice that received T. brucei total lysates were partly protected from developing severe malaria pathology. Interestingly, the presence of total lysates of T. brucei results in a decrease in the number of infected hepatocytes rather than from an impairment of intrahepatic replication of Plasmodium parasites. Surprisingly, the phenotype observed in this co-infection appears to be independent of liver damage and the of the host’simmune response. Biochemical characterization 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 and other GPI-anchored proteins. 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. Our study paves the way to the development of novel antiplasmodial intervention strategies, based on the mechanism involved during the co-infection between T. brucei and Plasmodium.engCo-infeçõesPlasmodiummaláriaTrypanosoma bruceiproteínas excretadasdoença do sonoVSGinfeção hepáticaCo-infectionsmalariaexcreted proteinssleeping sicknessliver infectiondoctoral thesis101616783