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Using immunoregulatory networks to prevent and decrease the burden of neglected tropical diseases

Visiting Academic. Walderez Ornelas Dutra, PhD. Cell-cell Interactions Lab - Federal University of Minas Gerais. Belo Horizonte - MG - Brazil

Professor Walderez Ornelas Dutra  

wal 18Visiting Academic

Professor Wal Dutra, a senior Brazilian researcher from the Federal University of Minas Gerais, is a specialist in human infectious and parasitic diseases, with a current focus on the immunology of human leishmaniasis (a neglected tropical disease). Her visit is very useful and timely for the WT-CCGHR, particularly for interacting with members of the Cambridge Parasitic & Neglected Diseases Network.  She is currently working on developing a collaboration between Africa, Brazil, Cambridge (ABC Network). Wal is also collaborating with Jenny Blackwell and will be at WT-CCGHR until October 2018.

 

Using immunoregulatory networks to prevent and decrease the burden of neglected tropical disease

Over the past nineteen years, Walderez's laboratory has been studying the cellular and molecular mechanisms involved in the differential clinical evolution of human diseases, focusing particularly on Chagas disease and American tegumentary leishmaniasis, two neglected tropical parasitic diseases caused by intracellular protozoansparasites, against which there are no vaccines available.

The Lab focuses on immunoregulatory networks in Chagas disease and leishmaniasis, to identify markers of disease progression, as well as of protective responses, to instruct much needed alternative therapies and preventive measures. A series of cellular, molecular and genomics tools are used in research.

Chagas disease

1. Caused by infection with Trypanosoma cruzi

2. Main forms of transmission are via the vector 
(“kissing bug”), blood transfusion and organ transplantation (in non-endemic countries) and by ingestion of contaminated juices (such as açaí and sugar cane in endemic regions)

3. “Re-emerging” disease 

4. Six million people infected worldwide; 60,000 in Europe;  1,200 in London (UK) and 70M people at risk. 

5. 10,000 deaths/year (mainly due to cardiac Chagas disease)

6. Economical burden of over 1billion dollars/year

American Tegumentary Leishmaniasis (New World) 

1. Caused by infection with Leishmania braziliensis (main cause in Brazil), L. amazonensis, L. panamensis andL. guyanensis

2. Transmitted via the bite of the sandfly

3. Increase in treatment-resistant forms

4. 10 million people infected worldwide, mostly in Latin America

5. 350 million people at risk

 

wal imageThe yin/yang of immunoregulatory networks

This figure depicts the involvement of cytokines, produced by specific cell populations, in the development of Chagas disease and tegumentary leishmaniasis. Upon infection, it is important to produce inflammatory cytokines such as IFN-gamma and TNF-alpha, which will activate macrophages to kill the intracellular parasites. If the initial inflammatory environment is controlled by the expression of anti-inflammatory cytokines such as IL-10, this may lead to a balanced response, and the maintenance of mild clinical forms. 

Recently, Wal's laboratory has identified target genes involved in the development of pathogenic forms of Chagas disease. In addition, they have identified cell populations and cytokines associated with pathology in Chagas disease and leishmaniasis, pointing to biomarkers of disease progression, as well as treatment efficacy. 

Publications

  1. Viana AG, Magalhães LMD, Giunchetti RC, Dutra WO, Gollob KJ. Infection of Human Monocytes with Leishmania infantumStrains Induces a Downmodulated Response when Compared with Infection with Leishmania braziliensis. Front Immunol. 2018 Jan 8;8:1896. doi: 10.3389/fimmu.2017.01896. eCollection 2017.
  2. Passos LS, Villani FN, Magalhães LM, Gollob KJ, Antonelli LR, Nunes MC, Dutra WO. Blocking of CD1d Decreases Trypanosoma cruzi-Induced Activation of CD4-CD8- T Cells and Modulates the Inflammatory Response in Patients With Chagas Heart Disease. J Infect Dis. 2016 Sep 15;214(6):935-44. doi: 10.1093/infdis/jiw266. Epub 2016 Jul 1.
  3. Magalhães LM, Viana A, Chiari E, Galvão LM, Gollob KJ, Dutra WO. Differential Activation of Human Monocytes and Lymphocytes by Distinct Strains of Trypanosoma cruzi.PLoS Negl Trop Dis. 2015 Jul 6;9(7):e0003816. doi: 10.1371/journal.pntd.0003816. eCollection 2015.
  4. Costa GC, da Costa Rocha MO, Moreira PR, Menezes CA, Silva MR, Gollob KJ, Dutra WO. Functional IL-10 gene polymorphism is associated with Chagas disease cardiomyopathy. J Infect Dis. 2009 Feb 1;199(3):451-4. doi: 10.1086/596061.
  5. Morgan DJ, Guimaraes LH, Machado PR, D'Oliveira A Jr, Almeida RP, Lago EL, Faria DR, Tafuri WL, Dutra WO, Carvalho EM. Cutaneous leishmaniasis during pregnancy: exuberant lesions and potential fetal complications. Clin Infect Dis. 2007 Aug 15;45(4):478-82. Epub 2007 Jul 5. 

Related links

Further information on bio and more publications  

Professor Dutra interview at University of Cambridge

Watch Professor Walderez Ornelas Dutra being interviewed on 1st May 2018

The Centre supports collaborative partnerships and scientific training activities in basic biomedical and health-related research. This is achieved through coordinated cross-faculty research across departments and research institutes in Cambridge including The Wellcome Trust Sanger Institute. 

 

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