Mobirise
Mobirise

Achieving new frontiers through trypanosomatid exosomes (TEx)) (Transformar o potencial dos exossomas de tripanossomatideos em novas oportunidades (TEx)) –
- EXOTRYPANO Refª PTDC/CVT-CVT/28908/2017

ABSTRACT

  • Background: Extracellular vesicles (EVs) are nanovesicles released to the extracellular environment by cells and also by pathogens. Transporting active macromolecules to the recipient cells, EVs have been associated with cell-to-cell communication processes. These vesicles seem to fuse with cell membranes or to be internalized by cells, either way, releasing cargo intracellularly. Cargo molecules can interfere in cell recognition and the pathway signaling, causing changes in the state of the cell. Trypanosomatids are the etiologic agents of the neglected zoonotic diseases like Leishmaniasis, African trypanosomiasis (Sleeping Sickness and Nagana, and American trypanosomiasis (Chagas Disease)and also shed EVs similar to higher eukaryotic cells. These parasitic diseases afflict human beings, domestic and wild animals.
  • Aim: The working hypothesis of the present proposal is that TEx can insert some modulation of the host immune response, reinforcing the chances of parasite survival in the mammal host and ensuring parasite availability to be naturally transmitted. Therefore, EXOTRYPANO’s main goal is to determine in vitro the effect of TEx in the functional activity of host immune cells.
  • Innovation: EXOTRYPANO uses cellular and molecular in vitro systems, which include innate and acquired immune cells to evaluate the effect of TEx on the immune response against parasitic infections. Findings will be further transposed for an interactive model that might lead to the development of novel immunotherapeutic tools applied to Leishmaniasis, Sleeping Sickness, Nagana, and Chagas Disease and eventually to other non-infectious diseases such as cancer and autoimmune diseases.
  • Expectations: Taking together the expertise of different academic research groups and institutions that participate in this research project, it is expected that EXOTRYPNO gives a powerful contribution to clarify the role of TEx, the non-infectious nanovesicles shed by Leishmania and Trypanosoma, in immune cells recognition and pathways induction, establishing a close picture of how and where these vesicles works and, weather can be further applied in redirecting the immune system, favoring the establishment of protective immune responses, being able to reduce the incidence of parasitic diseases, and thus contributing for healthiest society. It is also expected that EXOTRYPANO participates in student training and global open communication, improving science awareness of the strategic importance that the development of science and technology has in everyday life. 



PARTNERS

Instituto de Higiene e Medicina Tropical (IHMT), Universidade Nova de Lisboa (UNL), Lisbon, Portugal

Faculdade de Medicina Veterinária (FMV), CIISA–Centro de Investigação Interdisciplinar em Sanidade Animal, Universidade de Lisboa (ULisboa), Lisbon, Portugal,

Health Sciences Centre/Federal University of Rio Grande do Norte (UFRN, Natal, Brazil)


Do you want to reach us?  Please contact:

Prof. Gabriela Santos-Gomessantosgomes@ihmt.unl.pt
Global Health and Tropical Medicine, GHTM, Instituto de Higiene e Medicina Tropical, IHMT, Universidade Nova de Lisboa, UNL, Rua da Junqueira 100, 1349-008 Lisbon, Portugal

Prof. Isabel Pereira da Fonsecaifonseca@fmv.ulisboa.pt
CIISA, Centre for Interdisciplinary Research in Animal Health. Faculty of Veterinary Medicine, University of Lisbon, Av. Universidade Técnica, 1300-477 Lisbon, Portugal

Prof. Marcelo Silva
mssilva.ufrn@gmail.com
UFRN, Universidade Federal do Rio Grande do Norte, Campus Universitário - Lagoa Nova, Natal - RN, 59078-970, Brazil

PUBLICATIONS

Rodrigues AV, Valério-Bolas A, Alexandre-Pires G, Aires Pereira M, Nunes T, Ligeiro D, Pereira da Fonseca I, Santos-Gomes G. 2022. Zoonotic Visceral Leishmaniasis: New Insights on Innate Immune Response by Blood Macrophages and Liver Kupffer Cells to Leishmania infantum Parasites. Biology. 11(1):100. https://doi.org/10.3390/biology11010100

Available at:
https://www.mdpi.com/2079-7737/11/1/100/htm

Dias-Guerreiro, Tatiana, Joana Palma-Marques, Patrícia Mourata-Gonçalves, Graça Alexandre-Pires, Ana Valério-Bolas, Áurea Gabriel, Telmo Nunes, Wilson Antunes, Isabel P.d. Fonseca, Marcelo Sousa-Silva, and Gabriela Santos-Gomes. 2021. "African Trypanosomiasis: Extracellular Vesicles Shed by Trypanosoma brucei brucei Manipulate Host Mononuclear Cells" Biomedicines 9, no. 8: 1056. https://doi.org/10.3390/biomedicines9081056


Available at:
https://www.mdpi.com/2227-9059/9/8/1056/htm

Alexandre-Pires G, Santos M, Rodrigues A, Pereira MA, Gomes J, Diaz SA, Gomes L, Basso A, Reisinho A, Gomes J, Leal R, Correia J, Bolas A, Meireles J, Santos-GomesI G, and Pereira-da-Fonseca I . 2020. Leishmaniosis: New Insights in a Changing World. In: Freitas Duarte A., Lopes da Costa L. (eds) Advances in Animal Health, Medicine and Production. Springer, Cham. https://doi.org/10.1007/978-3-030-61981-7_17

Available at: https://link.springer.com/chapter/10.1007/978-3-030-61981-7_17

Santos MF, Alexandre-Pires G, Pereira MA, Gomes L, Rodrigues AV, Basso A, Reisinho A, Meireles J, Santos-Gomes GM and Pereira da Fonseca I. 2020. Immunophenotyping of Peripheral Blood, Lymph Node, and Bone Marrow T Lymphocytes During Canine Leishmaniosis and the Impact of Antileishmanial Chemotherapy. Front. Vet. Sci. 7:375. doi.org/10.3389/fvets.2020.00375

Available at: https://www.frontiersin.org/articles/10.3389/fvets.2020.00375/full

Rodrigues AV, Alexandre-Pires G, Valério-Bolas A, Santos-Mateus D, Rafael-Fernandes M, Pereira MA, Ligeiro D, Nunes T, Alves-Azevedo R, Santos M, Pereira da Fonseca I, Santos-Gomes G. 2020. 3D-Hepatocyte Culture Applied to Parasitology: Immune Activation of Canine Hepatic Spheroids Exposed to Leishmania infantum. Biomedicines. 18;8(12):628. doi: 10.3390/biomedicines8120628.

Available at:
https://www.mdpi.com/2227-9059/8/12/628/htm

Pereira M, Valério-Bolas A, Saraiva-Marques C, Alexandre-Pires G, Pereira da Fonseca I, Santos-Gomes G. 2019. Development of Dog Immune System: From in Uterus to Elderly. Vet Sci. 2019;6(4):83. doi:10.3390/vetsci6040083



Available at:
https://www.mdpi.com/2306-7381/6/4/83/htm

Gabriel Á, Valério-Bolas A, Palma-Marques J, Mourata-Gonçalves P, Ruas P, Dias-Guerreiro T, Santos-Gomes G. 2019. Cutaneous Leishmaniasis: The Complexity of Host's Effective Immune Response against a Polymorphic Parasitic Disease. J Immunol Res. 2019;2019:2603730. doi: 10.1155/2019/2603730

Available at: https://www.hindawi.com/journals/jir/2019/2603730/



ACADEMIC DEGREES

- Marcos André Ferreira Santos (2020) - "Cytokine gene expression and cellular immune response in dogs with leishmaniosis before and under the two first-line treatment protocols: new insights into the animal disease” – PhD Thesis. Faculty of Veterinary Medicine, University of Lisbon, 1 oct 2020, 205 pp. Supervisors: Prof. Isabel Pereira da Fonseca (FMV) and Prof. Gabriela Santos Gomes (IHMT).

- Cláudia Jéssica Gonçalves Moreno, (2020) - "Metaloproteinases de Tripanosomatídeos: Avaliação de potenciais inibidores como ferramenta para o desenvolvimento de fármacos." PhD thesis, Programa de Pós-Graduação em Bioquímica –UFRN (Natal, RGN, Brazil). Orientação: Doutor Marcelo de Sousa da Silva.

- Catarina Isabel Lopes Sequeira (2021) - "Leishmania spp. infection/Leishmaniosis in cats from Península de Setúbal." Dissertação de Mestrado Integrado em Medicina Veterinária. Faculdade de Medicnia Veterinaria, Universidade de Lisboa. 15 fev 2021. Orientação: Prof. Isabel Pereira da Fonseca.

- Joana Barbosa (2021)  - “Detection of anti-Leishmania antibodies in dog sera from Mozambique, Angola and Cape Verde subjected to evaluation of the efficacy of rabies vaccination”. Integrated Master in Veterinary Medicine. FMV/Ulisboa. Supervisor: Isabel Pereira da Fonseca. On going.

- Mafalda Pinto (2020) - “Ecological drivers of Leishmania infantum detection and characterization in endogenous wild mammals in Portugal: mongoose (Herpestes ichneumon) and red fox (Vulpes vulpes)”. Master in Human Biology and Environment, FCUL. Co-supervisor: Isabel Pereira da Fonseca. On going.

- Vera Laranjo (2021) - “Detection of anti-Leishmania antibodies in rodents, lagomorphs and mustelids pets, in the Lisbon Metropolitan Area”. Integrated Master in Veterinary Medicine. FMV/Ulisboa. Supervisor: Isabel Pereira da Fonseca. On going.

- George Nakhratyan (2021) - “Unravel the immunomodulatory potential of exosomes of cutaneous Leishmania spp. using an in vitro cellular model of skin”, Master Thesis, NOVA School of Science and Technology. Supervisor: Armanda Rodrigues and Co-supervisor - Gabriela Santos-Gomes.

- Juliana Weber (2021) - “Efeito da vesiculas extracelulares de espécies cutâneas de Leishmania em macrófagos de murganho”, Master Thesis, Instituto de Higiene e Medicina Tropical (IHMT/NOVA). Supervisor: Gabriela Santos-Gomes and Co-supervisor: Armanda Rodrigues.

- Flávia Martins (2022) - “Efeito de vesículas extracelulares de Leishmania spp. na actividade funcional de leucócitos caninos” . Master Thesis, Instituto de Higiene e Medicina Tropical (IHMT/NOVA). Supervisor: Armanda Rodrigues and Co-supervisor - Gabriela Santos-Gomes.

- Bruna Freitas (2021) - “Vesículas extracelulares de Leishmania amazonensis: activação de macrófagos murinos e antigenicidade” Master Thesis, Instituto de Higiene e Medicina Tropical (IHMT/NOVA). Supervisor: Gabriela Santos-Gomes.

TRAINING

Mafalda Meunier
Juliana Weber
George Nakhratyan
Flávia Martins
Bruna Freitas
Sofia Gabriel

NEWS


1st seminar on “New approaches to tackle trypanosomiasis” to be hosted by IHMT, as a World Health Organization (WHO) Collaborative Centre (CCol), predicted to take place in 2022. More information soon. 

The EXOTRYPANO Team has new publications, available in open access:

Rodrigues AV, Valério-Bolas A, Alexandre-Pires G, Aires Pereira M, Nunes T, Ligeiro D, Pereira da Fonseca I, Santos-Gomes G. 2022. Zoonotic Visceral Leishmaniasis: New Insights on Innate Immune Response by Blood Macrophages and Liver Kupffer Cells to Leishmania infantum Parasites. Biology. 11(1):100. https://doi.org/10.3390/biology11010100

Dias-Guerreiro, Tatiana, Joana Palma-Marques, Patrícia Mourata-Gonçalves, Graça Alexandre-Pires, Ana Valério-Bolas, Áurea Gabriel, Telmo Nunes, Wilson Antunes, Isabel P.d. Fonseca, Marcelo Sousa-Silva, and Gabriela Santos-Gomes. 2021. "African Trypanosomiasis: Extracellular Vesicles Shed by Trypanosoma brucei brucei Manipulate Host Mononuclear Cells" Biomedicines 9, no. 8: 1056. https://doi.org/10.3390/biomedicines9081056

Post-doctoral researcher Claudia Jassica Gonçalves Moreno, member of the EXOTRYPANO TEAM (UFRN) has won a honourable mention on Capes 2021 edition “ Prêmio de Teses da Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Capes) da edição 2021”. Claudia was supervised by professor Marcelo de Sousa da Silva.
More information at: https://ufrn.br/imprensa/noticias/50772/cinco-teses-da-ufrn-sao-premiados-pela-capes




The Worldleish 7 Congress, will take place in Cartagena, Colombia.  

Life under the microscope

Mobirise

Caption 1:

Leishmania shawi promastigotes. Scan electron microscopy (SEM) image. The parasite has an elongated body and a visible flagellum (Alexandre-Pires, G.)

Mobirise

Caption 2:

Canine blood-macrophages (magnification 400x). Optical microscopy with no staining. (Rodrigues, MA).


EXOTRYPANO is a Portugal-Brazil partnership research project raised to decipher the communication established by extracellular nanovesicles shed by trypanosomatids with host immune cells in the next three years.

EXOTRYPANO brings together renowned experts of three academic institutions from Portugal, IHMT-NOVA and FMV-ULisboa (Lisbon), and from Brazil, UFRN (Natal, RGN) This interdisciplinary project will explore the mechanisms used by extracellular nanovesicles emitted by Leishmania, Trypanosoma cruzi, and Trypanosoma brucei to influence the host immune response. This research project aims to contribute to improving treatment and control of Leishmaniasis, Chagas Disease, and African trypanosomiasis, which are parasitic diseases that afflict human populations and animals across the globe, especially in Africa and South America. The Portuguese Foundation for Science and Technology (FCT) supports the activities of this academic research initiative.

Mobirise

Vector-borne parasitic diseases significantly affect the well-being of millions of people around the globe, especially in low-income countries, posing a substantial burden to healthcare systems, and also causes disease in domestic and wild animals. African human 

trypanosomiasis or sleeping sickness and African animal trypanosomiasis or nagana caused by T. brucei are found in the sub-Sahara region. This animal parasitic disease, which affects cattle, is recognized as a major obstacle for economical development. In Central and South America, T. cruzi causes American trypanosomiasis or Chagas disease in humans, wild and domestic animals, including dogs and cats, is a major public health problem. Currently, this neglected tropical disease is spreading to other areas, constituting an emerging disease of global concern. Presenting a worldwide dispersion, with the exception of Australia, the Pacific Islands, and Antarctica, Leishmaniasis is caused by Leishmania also transmitted by blood-sucking arthropods, affecting humans and canids, especially dogs. For these neglected diseases, mainly associated with poor living conditions therapy has long been a challenge and prophylactic vaccines have only become available for canine leishmaniasis.

EXOTRYPANO integrates cellular and immune methodologies as well as transcriptomic and high-throughput image technology to identify the relationship between trypanosomatid extracellular vesicles and host immune. All data generated within this project will be centralized, enabling detailed and comprehensive bioinformatics and biostatistics analyses.  

EXOTRYPANO intends to increase the fundamental knowledge on the molecular pathways tackled by trypanosomatid extracellular vesicles in parallel in three parasitic diseases; Leishmaniasis, American Trypanosomiasis or Chagas disease and African Trypanosomiasis (sleeping sickness and nagana). A common pattern on the effect of parasite extracellular nanovesicles may be found across these diseases, indicating that they may share immunopathogenic pathways, identifying biomarkers that can help in improving patient management and disease prevention.

EXOTRYPANO activities were formally open with a launching meeting that took place at IHMT-NOVA (Lisbon, Portugal) on January 29, 2020. 

Mobirise

Web page was created with Mobirise