Excreted Trypanosoma brucei proteins inhibit Plasmodium hepatic infection

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. b...

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Autores principales:	Adriana Temporão, Margarida Sanches-Vaz, Rafael Luís, Helena Nunes-Cabaço, Terry K. Smith, Miguel Prudêncio, Luisa M. Figueiredo
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270
Acceso en línea:	https://doaj.org/article/5eaf28c1c3664433b188f94e8f25947e
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spelling	oai:doaj.org-article:5eaf28c1c3664433b188f94e8f25947e2021-11-18T09:12:18ZExcreted Trypanosoma brucei proteins inhibit Plasmodium hepatic infection1935-27271935-2735https://doaj.org/article/5eaf28c1c3664433b188f94e8f25947e2021-10-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8580256/?tool=EBIhttps://doaj.org/toc/1935-2727https://doaj.org/toc/1935-2735Malaria, 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. Author summary Malaria and sleeping sickness are parasitic illnesses that overlap geographically, making it likely that co-infections between the two causative parasites occur. It was previously shown that when mice are first infected with Trypanosoma brucei, there was an attenuation of the subsequent infection by Plasmodium. 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 not only T. brucei total lysates are able to inhibit Plasmodium liver infection, but also that mice that received these lysates are partly protected from developing severe malaria pathology. We further showed that this protective effect is mediated by proteins excreted by trypanosomes. 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.Adriana TemporãoMargarida Sanches-VazRafael LuísHelena Nunes-CabaçoTerry K. SmithMiguel PrudêncioLuisa M. FigueiredoPublic Library of Science (PLoS)articleArctic medicine. Tropical medicineRC955-962Public aspects of medicineRA1-1270ENPLoS Neglected Tropical Diseases, Vol 15, Iss 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270
spellingShingle	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Adriana Temporão Margarida Sanches-Vaz Rafael Luís Helena Nunes-Cabaço Terry K. Smith Miguel Prudêncio Luisa M. Figueiredo Excreted Trypanosoma brucei proteins inhibit Plasmodium hepatic infection
description	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. Author summary Malaria and sleeping sickness are parasitic illnesses that overlap geographically, making it likely that co-infections between the two causative parasites occur. It was previously shown that when mice are first infected with Trypanosoma brucei, there was an attenuation of the subsequent infection by Plasmodium. 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 not only T. brucei total lysates are able to inhibit Plasmodium liver infection, but also that mice that received these lysates are partly protected from developing severe malaria pathology. We further showed that this protective effect is mediated by proteins excreted by trypanosomes. 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.
format	article
author	Adriana Temporão Margarida Sanches-Vaz Rafael Luís Helena Nunes-Cabaço Terry K. Smith Miguel Prudêncio Luisa M. Figueiredo
author_facet	Adriana Temporão Margarida Sanches-Vaz Rafael Luís Helena Nunes-Cabaço Terry K. Smith Miguel Prudêncio Luisa M. Figueiredo
author_sort	Adriana Temporão
title	Excreted Trypanosoma brucei proteins inhibit Plasmodium hepatic infection
title_short	Excreted Trypanosoma brucei proteins inhibit Plasmodium hepatic infection
title_full	Excreted Trypanosoma brucei proteins inhibit Plasmodium hepatic infection
title_fullStr	Excreted Trypanosoma brucei proteins inhibit Plasmodium hepatic infection
title_full_unstemmed	Excreted Trypanosoma brucei proteins inhibit Plasmodium hepatic infection
title_sort	excreted trypanosoma brucei proteins inhibit plasmodium hepatic infection
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/5eaf28c1c3664433b188f94e8f25947e
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Excreted Trypanosoma brucei proteins inhibit Plasmodium hepatic infection

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