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.
Highlights
The term co-infection describes the co-existence of two or more infectious agents in the same host [1], an event that occurs when that host is infected by different pathogens
It was previously shown that when mice are first infected with Trypanosoma brucei, there was an attenuation of the subsequent infection by Plasmodium
We found that T. brucei total lysates are able to inhibit Plasmodium liver infection, and that mice that received these lysates are partly protected from developing severe malaria pathology
Summary
The term co-infection describes the co-existence of two or more infectious agents in the same host [1], an event that occurs when that host is infected by different pathogens. Humans become infected once an infected female Anopheles mosquito takes a blood meal, injecting sporozoites into the host’s skin These sporozoites reach the blood circulation and travel to the liver, where they cross endothelium sinusoids and traverse several liver cells until they effectively infect one. Sporozoites differentiate into exoerythrocytic forms (EEFs) that originate thousands of merozoites These newly formed parasites egress from the hepatocytes and infect red blood cells, thereby initiating the blood stage of the Plasmodium infection [5]. Several liver cells, including Kupffer cells, are exposed to parasite antigens and may present them to lymphocytes [10, 11]
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