African Trypanosomiasis: Extracellular Vesicles Shed by <i>Trypanosoma brucei brucei</i> Manipulate Host Mononuclear Cells
African trypanosomiasis or sleeping sickness is a zoonotic disease caused by <i>Trypanosoma brucei</i>, a protozoan parasite transmitted by <i>Glossina</i> spp. (tsetse fly). Parasite introduction into mammal hosts triggers a succession of events, involving both innate and ad...
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MDPI AG
2021-08-01
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author | Tatiana Dias-Guerreiro Joana Palma-Marques Patrícia Mourata-Gonçalves Graça Alexandre-Pires Ana Valério-Bolas Áurea Gabriel Telmo Nunes Wilson Antunes Isabel Pereira da Fonseca Marcelo Sousa-Silva Gabriela Santos-Gomes |
author_facet | Tatiana Dias-Guerreiro Joana Palma-Marques Patrícia Mourata-Gonçalves Graça Alexandre-Pires Ana Valério-Bolas Áurea Gabriel Telmo Nunes Wilson Antunes Isabel Pereira da Fonseca Marcelo Sousa-Silva Gabriela Santos-Gomes |
author_sort | Tatiana Dias-Guerreiro |
collection | DOAJ |
description | African trypanosomiasis or sleeping sickness is a zoonotic disease caused by <i>Trypanosoma brucei</i>, a protozoan parasite transmitted by <i>Glossina</i> spp. (tsetse fly). Parasite introduction into mammal hosts triggers a succession of events, involving both innate and adaptive immunity. Macrophages (MΦ) have a key role in innate defence since they are antigen-presenting cells and have a microbicidal function essential for trypanosome clearance. Adaptive immune defence is carried out by lymphocytes, especially by T cells that promote an integrated immune response. Like mammal cells, <i>T. b. brucei</i> parasites release extracellular vesicles (TbEVs), which carry macromolecules that can be transferred to host cells, transmitting biological information able to manipulate cell immune response. However, the exact role of TbEVs in host immune response remains poorly understood. Thus, the current study examined the effect elicited by TbEVs on MΦ and T lymphocytes. A combined approach of microscopy, nanoparticle tracking analysis, multiparametric flow cytometry, colourimetric assays and detailed statistical analyses were used to evaluate the influence of TbEVs in mouse mononuclear cells. It was shown that TbEVs can establish direct communication with cells of innate and adaptative immunity. TbEVs induce the differentiation of both M1- and M2-MΦ and elicit the expansion of MHCI<sup>+</sup>, MHCII<sup>+</sup> and MHCI<sup>+</sup>MHCII<sup>+</sup> MΦ subpopulations. In T lymphocytes, TbEVs drive the overexpression of cell-surface CD3 and the nuclear factor FoxP3, which lead to the differentiation of regulatory CD4<sup>+</sup> and CD8<sup>+</sup> T cells. Moreover, this study indicates that <i>T. b. brucei</i> and TbEVs seem to display opposite but complementary effects in the host, establishing a balance between parasite growth and controlled immune response, at least during the early phase of infection. |
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spelling | doaj.art-7daa4ce9e6e8472399d4461aab9a17b32023-11-22T06:53:59ZengMDPI AGBiomedicines2227-90592021-08-0198105610.3390/biomedicines9081056African Trypanosomiasis: Extracellular Vesicles Shed by <i>Trypanosoma brucei brucei</i> Manipulate Host Mononuclear CellsTatiana Dias-Guerreiro0Joana Palma-Marques1Patrícia Mourata-Gonçalves2Graça Alexandre-Pires3Ana Valério-Bolas4Áurea Gabriel5Telmo Nunes6Wilson Antunes7Isabel Pereira da Fonseca8Marcelo Sousa-Silva9Gabriela Santos-Gomes10Global Health and Tropical Medicine (GHTM), Instituto de Higiene e Medicina Tropical (IHMT), Universidade Nova de Lisboa (UNL), 1349-008 Lisboa, PortugalGlobal Health and Tropical Medicine (GHTM), Instituto de Higiene e Medicina Tropical (IHMT), Universidade Nova de Lisboa (UNL), 1349-008 Lisboa, PortugalGlobal Health and Tropical Medicine (GHTM), Instituto de Higiene e Medicina Tropical (IHMT), Universidade Nova de Lisboa (UNL), 1349-008 Lisboa, PortugalCentro de Investigação Interdisciplinar em Sanidade Animal, Faculdade de Medicina Veterinária, Universidade de Lisboa, 1300-477 Lisboa, PortugalGlobal Health and Tropical Medicine (GHTM), Instituto de Higiene e Medicina Tropical (IHMT), Universidade Nova de Lisboa (UNL), 1349-008 Lisboa, PortugalGlobal Health and Tropical Medicine (GHTM), Instituto de Higiene e Medicina Tropical (IHMT), Universidade Nova de Lisboa (UNL), 1349-008 Lisboa, PortugalMicroscopy Center, Faculty of Sciences, University of Lisbon, Campo Grande, 1749-016 Lisboa, PortugalUnidade Militar Laboratorial de Defesa Biológica e Química (UMLDBQ), Laboratório de Imagem Nano-Morfológica e Espectroscopia de Raios-X, 1100-471 Lisboa, PortugalCentro de Investigação Interdisciplinar em Sanidade Animal, Faculdade de Medicina Veterinária, Universidade de Lisboa, 1300-477 Lisboa, PortugalGlobal Health and Tropical Medicine (GHTM), Instituto de Higiene e Medicina Tropical (IHMT), Universidade Nova de Lisboa (UNL), 1349-008 Lisboa, PortugalGlobal Health and Tropical Medicine (GHTM), Instituto de Higiene e Medicina Tropical (IHMT), Universidade Nova de Lisboa (UNL), 1349-008 Lisboa, PortugalAfrican trypanosomiasis or sleeping sickness is a zoonotic disease caused by <i>Trypanosoma brucei</i>, a protozoan parasite transmitted by <i>Glossina</i> spp. (tsetse fly). Parasite introduction into mammal hosts triggers a succession of events, involving both innate and adaptive immunity. Macrophages (MΦ) have a key role in innate defence since they are antigen-presenting cells and have a microbicidal function essential for trypanosome clearance. Adaptive immune defence is carried out by lymphocytes, especially by T cells that promote an integrated immune response. Like mammal cells, <i>T. b. brucei</i> parasites release extracellular vesicles (TbEVs), which carry macromolecules that can be transferred to host cells, transmitting biological information able to manipulate cell immune response. However, the exact role of TbEVs in host immune response remains poorly understood. Thus, the current study examined the effect elicited by TbEVs on MΦ and T lymphocytes. A combined approach of microscopy, nanoparticle tracking analysis, multiparametric flow cytometry, colourimetric assays and detailed statistical analyses were used to evaluate the influence of TbEVs in mouse mononuclear cells. It was shown that TbEVs can establish direct communication with cells of innate and adaptative immunity. TbEVs induce the differentiation of both M1- and M2-MΦ and elicit the expansion of MHCI<sup>+</sup>, MHCII<sup>+</sup> and MHCI<sup>+</sup>MHCII<sup>+</sup> MΦ subpopulations. In T lymphocytes, TbEVs drive the overexpression of cell-surface CD3 and the nuclear factor FoxP3, which lead to the differentiation of regulatory CD4<sup>+</sup> and CD8<sup>+</sup> T cells. Moreover, this study indicates that <i>T. b. brucei</i> and TbEVs seem to display opposite but complementary effects in the host, establishing a balance between parasite growth and controlled immune response, at least during the early phase of infection.https://www.mdpi.com/2227-9059/9/8/1056African trypanosomiasis<i>Trypanosoma brucei brucei</i>exosomesmacrophagesT lymphocytesregulatory T cells |
spellingShingle | Tatiana Dias-Guerreiro Joana Palma-Marques Patrícia Mourata-Gonçalves Graça Alexandre-Pires Ana Valério-Bolas Áurea Gabriel Telmo Nunes Wilson Antunes Isabel Pereira da Fonseca Marcelo Sousa-Silva Gabriela Santos-Gomes African Trypanosomiasis: Extracellular Vesicles Shed by <i>Trypanosoma brucei brucei</i> Manipulate Host Mononuclear Cells Biomedicines African trypanosomiasis <i>Trypanosoma brucei brucei</i> exosomes macrophages T lymphocytes regulatory T cells |
title | African Trypanosomiasis: Extracellular Vesicles Shed by <i>Trypanosoma brucei brucei</i> Manipulate Host Mononuclear Cells |
title_full | African Trypanosomiasis: Extracellular Vesicles Shed by <i>Trypanosoma brucei brucei</i> Manipulate Host Mononuclear Cells |
title_fullStr | African Trypanosomiasis: Extracellular Vesicles Shed by <i>Trypanosoma brucei brucei</i> Manipulate Host Mononuclear Cells |
title_full_unstemmed | African Trypanosomiasis: Extracellular Vesicles Shed by <i>Trypanosoma brucei brucei</i> Manipulate Host Mononuclear Cells |
title_short | African Trypanosomiasis: Extracellular Vesicles Shed by <i>Trypanosoma brucei brucei</i> Manipulate Host Mononuclear Cells |
title_sort | african trypanosomiasis extracellular vesicles shed by i trypanosoma brucei brucei i manipulate host mononuclear cells |
topic | African trypanosomiasis <i>Trypanosoma brucei brucei</i> exosomes macrophages T lymphocytes regulatory T cells |
url | https://www.mdpi.com/2227-9059/9/8/1056 |
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