Walderez Dutra

Walderez Dutra

Professor of Cell Biology 

Dept. Morphology, Federal University of Minas Gerais,  Belo Horizonte, Brazil

Tel: +55-31-99102-1930

Email: waldutra@gmail.com

 

 

 

 

VALIDATE Role:

Network Investigator

Research Keywords: 

Leishmania, T-cells, immunoregulation, immunopathology, human 

Biography:
Our 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 protozoans parasites, against which there are no vaccines available.

We focus our studies in 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. We use a series of cellular, molecular and genomics tools to address our questions. Both T. cruzi and Leishmania sp. directly interfere with the immune response, as they parasitize macrophages and other antigen-presenting cells. While infection triggers an inflammatory response, which is needed to eliminate the parasites, the subsequent control of this initial response is needed to avoid tissue destruction and pathology establishment. The inability to perform such immunological control has been associated with the establishment of severe forms of these diseases. Thus, identifying the mechanisms involved in the triggering and control (or lack of it) of the immune response is key for disease prevention and for interfering with disease progression. 

Recently, our laboratory has identified target genes involved in the development of pathogenic forms of Chagas disease. In addition, we 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. Some of these findings have helped in designing alternative therapies, which have shown efficacy in severe and resistant forms, emphasizing the translational approach of our research. While continuing our research, we now hope to use the results obtained over the years to form a robust database for modelling of the immune response associated with these diseases, bringing new insights to the understanding of disease dynamics, progression and susceptibility.  
  

The yin/yang of immunoregulatory networks

The 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. However, the inability to further control the initial inflammatory response seems to be associated with the establishment of severe clinical forms of the diseases. Dissecting the mechanisms that underlie these interactions emerges as a key aspect to interfere with disease progression and severity. 
 

Related Websites: 

LinkedIn

 

Key Publications: 

Léa C. Castellucci, Lucas Almeida, Svetlana Cherlin, Michaela Fakiola, Edgar Carvalho, Amanda B. Figueiredo, Clara M. Cavalcanti, Natalia S. 

Alves, Walderez O. Dutra, Kenneth J. Gollob, Heather J. Cordell, Jenefer M. Blackwell A genome-wide association study highlights a regulatory role for IFNG-AS1 contributing to cutaneous leishmaniasis in Brazil. 2020 doi: https://doi.org/10.1101/2020.01.13.903989 in BioRxiv. 
 
Dutra WO, Barbosa DF, de Souza PEA, Morgan D, Poetker S, Guimarães LH, Bacelar O, Gollob KJ, Carvalho EM. A Th2-Type Response Is Associated With Exuberant Lesions in Pregnant Women Infected With Leishmania braziliensis. J Infect Dis. 2019 Jan 9;219(3):480-488. doi: 10.1093/infdis/jiy510. 
 
Faria DR, Barbieri LC, Koh CC, Machado PRL, Barreto CC, Lima CMF, Lessa MM, Carvalho E, Gollob KJ, Dutra WO. In Situ Cellular Response Underlying Successful Treatment of Mucosal Leishmaniasis with a Combination of Pentavalent Antimonial and Pentoxifylline. Am J Trop Med Hyg. 2019 Aug;101(2):392-401. doi: 10.4269/ajtmh.19-0139. 
 
Viana AG, Magalhães LMD, Giunchetti RC, Dutra WO, Gollob KJ. Leishmania infantum induces expression of the negative regulatory checkpoint, CTLA-4, by human naïve CD8+ T cells. Parasite Immunol. 2019 Sep;41(9):e12659. doi: 10.1111/pim.12659.  
 
Viana AG, Magalhães LMD, Giunchetti RC, Dutra WO, Gollob KJ. Infection of Human Monocytes with Leishmania infantum Strains 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. 
 
Gonçalves AAM, Leite JC, Resende LA, Mariano RMDS, Silveira P, MeloJúnior OAO, Ribeiro HS, de Oliveira DS, Soares DF, Santos TAP, Marques AF, Galdino AS, Martins-Filho OA, Dutra WO, da Silveira-Lemos D, Giunchetti RC. An Overview of Immunotherapeutic Approaches Against Canine Visceral Leishmaniasis: What Has Been Tested on Dogs and a New Perspective on Improving Treatment Efficacy. Front Cell Infect Microbiol. 2019 Dec 18;9:427. doi: 10.3389/fcimb.2019.00427. 
 
Gollob KJ, Viana AG, Dutra WO. Immunoregulation in human American leishmaniasis: balancing pathology and protection. Parasite Immunol. 2014 Aug;36(8):367-76. doi: 10.1111/pim.12100. Review. 
 
Faria DR, Souza PE, Durães FV, Carvalho EM, Gollob KJ, Machado PR, Dutra WO. Recruitment of CD8(+) T cells expressing granzyme A is associated with lesion progression in human cutaneous leishmaniasis. Parasite Immunol. 2009 Aug;31(8):432-9. doi: 10.1111/j.13653024.2009.01125.x. 
 
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.  
 
Faria DR, Gollob KJ, Barbosa J Jr, Schriefer A, Machado PR, Lessa H, Carvalho LP, Romano-Silva MA, de Jesus AR, Carvalho EM, Dutra WO.