Search

© 2021 Temporão et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited., 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., This work was supported by the Howard Hughes Medical Institute (ref. 55007419) awarded to LMF, by Fundação para a Ciência e Tecnologia (PD/BD/138891/2018) awarded to AT, (PD/BD/105838/2018) awarded to MSV, (CEECIND/03322/2018) awarded to LMF, (CEECIND/03539/2017) awarded to MP, and by the Wellcome Trust (094476/Z/10/Z) awarded to TKS.

International audience; Hydrogenases are metalloenzymes that catalyse both H(2)evolution and uptake. They are gas-processing enzymes with deeply buried active sites, so the gases diffuse through channels that connect the active site to the protein surface. The [NiFeSe] hydrogenases are a special class of hydrogenases containing a selenocysteine as a nickel ligand; they are more catalytically active and less O-2-sensitive than standard [NiFe] hydrogenases. Characterisation of the channel system of hydrogenases is important to understand how the inhibitor oxygen reaches the active site to cause oxidative damage. To this end, crystals ofDesulfovibrio vulgarisHildenborough [NiFeSe] hydrogenase were pressurized with krypton and oxygen, and a method for tracking labile O(2)molecules was developed, for mapping a hydrophobic channel system similar to that of the [NiFe] enzymes as the major route for gas diffusion.

Sleeping sickness and malaria are parasitic diseases with overlapping geographical distributions in sub-Saharan Africa. We hypothesized that the immune response elicited by an infection with Trypanosoma brucei, the etiological agent of sleeping sickness, would inhibit a subsequent infection by Plasmodium, the malaria parasite, decreasing the severity of its associated pathology. To investigate this, we established a new co-infection model in which mice were initially infected with T. brucei, followed by administration of P. berghei sporozoites. We observed that a primary infection by T. brucei significantly attenuates a subsequent infection by the malaria parasite, protecting mice from experimental cerebral malaria and prolonging host survival. We further observed that an ongoing T. brucei infection leads to an accumulation of lymphocyte-derived IFN-γ in the liver, limiting the establishment of a subsequent hepatic infection by P. berghei sporozoites. Thus, we identified a novel host-mediated interaction between two parasitic infections, which may be epidemiologically relevant in regions of Trypanosoma/Plasmodium co-endemicity., Author summary Despite the geographical overlap between the parasites that cause sleeping sickness and malaria, the reciprocal impact of a co-infection by T. brucei and Plasmodium had hitherto not been assessed. We hypothesized that the strong immune response elicited by a T. brucei infection could potentially limit the ability of Plasmodium parasites to infect the same host. In this study, we showed that a primary infection by T. brucei significantly attenuates a subsequent infection by the malaria parasite. Importantly, a significant proportion of the co-infected mice do not develop Plasmodium parasitemia, and those few that do, do not display symptoms of severe malaria and survive longer than their singly infected counterparts. We further showed that the prevention or delay in appearance of malaria parasites in the blood results from a dramatic impairment of the preceding liver infection by Plasmodium, which is mediated by the strong immune response mounted against the primary T. brucei infection. Our study provides new insights for a novel inter-pathogen interaction that may bear great epidemiological significance in regions of Trypanosoma/Plasmodium co-endemicity.

The protozoan Trypanosoma brucei, responsible for animal and human trypanosomiasis, has a family of major surface proteases (MSPs) and phospholipase-C (PLC), both involved in some mechanisms of virulence during mammalian infections. During parasitism in the mammalian host, this protozoan is exclusively extracellular and presents a robust mechanism of antigenic variation that allows the persistence of infection. There has been incredible progress in our understanding of how variable surface glycoproteins (VSGs) are organised and expressed, and how expression is switched, particularly through recombination. The objective of this manuscript is to create a reflection about the mechanisms of antigenic variation in T. brucei, more specifically, in the process of variable surface glycoprotein (VSG) release. We firstly explore the mechanism of VSG release as a potential pathway and target for the development of anti-T. brucei drugs.