Trypanosoma brucei triggers a broad immune response in the adipose tissue.

Adipose tissue is one of the major reservoirs of Trypanosoma brucei parasites, the causative agent of sleeping sickness, a fatal disease in humans. In mice, the gonadal adipose tissue (AT) typically harbors 2-5 million parasites, while most solid organs show 10 to 100-fold fewer parasites. In this s...

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Autores principales:	Henrique Machado, Tiago Bizarra-Rebelo, Mariana Costa-Sequeira, Sandra Trindade, Tânia Carvalho, Filipa Rijo-Ferreira, Barbara Rentroia-Pacheco, Karine Serre, Luisa M Figueiredo
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/694210f67c1c4fe59a45f9a34542278f
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spelling	oai:doaj.org-article:694210f67c1c4fe59a45f9a34542278f2021-12-02T20:00:11ZTrypanosoma brucei triggers a broad immune response in the adipose tissue.1553-73661553-737410.1371/journal.ppat.1009933https://doaj.org/article/694210f67c1c4fe59a45f9a34542278f2021-09-01T00:00:00Zhttps://doi.org/10.1371/journal.ppat.1009933https://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Adipose tissue is one of the major reservoirs of Trypanosoma brucei parasites, the causative agent of sleeping sickness, a fatal disease in humans. In mice, the gonadal adipose tissue (AT) typically harbors 2-5 million parasites, while most solid organs show 10 to 100-fold fewer parasites. In this study, we tested whether the AT environment responds immunologically to the presence of the parasite. Transcriptome analysis of T. brucei infected adipose tissue revealed that most upregulated host genes are involved in inflammation and immune cell functions. Histochemistry and flow cytometry confirmed an increasingly higher number of infiltrated macrophages, neutrophils and CD4+ and CD8+ T lymphocytes upon infection. A large proportion of these lymphocytes effectively produce the type 1 effector cytokines, IFN-γ and TNF-α. Additionally, the adipose tissue showed accumulation of antigen-specific IgM and IgG antibodies as infection progressed. Mice lacking T and/or B cells (Rag2-/-, Jht-/-), or the signature cytokine (Ifng-/-) displayed a higher parasite load both in circulation and in the AT, demonstrating the key role of the adaptive immune system in both compartments. Interestingly, infections of C3-/- mice showed that while complement system is dispensable to control parasite load in the blood, it is necessary in the AT and other solid tissues. We conclude that T. brucei infection triggers a broad and robust immune response in the AT, which requires the complement system to locally reduce parasite burden.Henrique MachadoTiago Bizarra-RebeloMariana Costa-SequeiraSandra TrindadeTânia CarvalhoFilipa Rijo-FerreiraBarbara Rentroia-PachecoKarine SerreLuisa M FigueiredoPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 17, Iss 9, p e1009933 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Henrique Machado Tiago Bizarra-Rebelo Mariana Costa-Sequeira Sandra Trindade Tânia Carvalho Filipa Rijo-Ferreira Barbara Rentroia-Pacheco Karine Serre Luisa M Figueiredo Trypanosoma brucei triggers a broad immune response in the adipose tissue.
description	Adipose tissue is one of the major reservoirs of Trypanosoma brucei parasites, the causative agent of sleeping sickness, a fatal disease in humans. In mice, the gonadal adipose tissue (AT) typically harbors 2-5 million parasites, while most solid organs show 10 to 100-fold fewer parasites. In this study, we tested whether the AT environment responds immunologically to the presence of the parasite. Transcriptome analysis of T. brucei infected adipose tissue revealed that most upregulated host genes are involved in inflammation and immune cell functions. Histochemistry and flow cytometry confirmed an increasingly higher number of infiltrated macrophages, neutrophils and CD4+ and CD8+ T lymphocytes upon infection. A large proportion of these lymphocytes effectively produce the type 1 effector cytokines, IFN-γ and TNF-α. Additionally, the adipose tissue showed accumulation of antigen-specific IgM and IgG antibodies as infection progressed. Mice lacking T and/or B cells (Rag2-/-, Jht-/-), or the signature cytokine (Ifng-/-) displayed a higher parasite load both in circulation and in the AT, demonstrating the key role of the adaptive immune system in both compartments. Interestingly, infections of C3-/- mice showed that while complement system is dispensable to control parasite load in the blood, it is necessary in the AT and other solid tissues. We conclude that T. brucei infection triggers a broad and robust immune response in the AT, which requires the complement system to locally reduce parasite burden.
format	article
author	Henrique Machado Tiago Bizarra-Rebelo Mariana Costa-Sequeira Sandra Trindade Tânia Carvalho Filipa Rijo-Ferreira Barbara Rentroia-Pacheco Karine Serre Luisa M Figueiredo
author_facet	Henrique Machado Tiago Bizarra-Rebelo Mariana Costa-Sequeira Sandra Trindade Tânia Carvalho Filipa Rijo-Ferreira Barbara Rentroia-Pacheco Karine Serre Luisa M Figueiredo
author_sort	Henrique Machado
title	Trypanosoma brucei triggers a broad immune response in the adipose tissue.
title_short	Trypanosoma brucei triggers a broad immune response in the adipose tissue.
title_full	Trypanosoma brucei triggers a broad immune response in the adipose tissue.
title_fullStr	Trypanosoma brucei triggers a broad immune response in the adipose tissue.
title_full_unstemmed	Trypanosoma brucei triggers a broad immune response in the adipose tissue.
title_sort	trypanosoma brucei triggers a broad immune response in the adipose tissue.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/694210f67c1c4fe59a45f9a34542278f
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Trypanosoma brucei triggers a broad immune response in the adipose tissue.

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