Please use this identifier to cite or link to this item:
https://www.arca.fiocruz.br/handle/icict/50219
Type
ArticleCopyright
Open access
Sustainable Development Goals
03 Saúde e Bem-EstarCollections
Metadata
Show full item record5
CITATIONS
5
Total citations
3
Recent citations
0.91
Field Citation Ratio
0.36
Relative Citation Ratio
THE BLOCKADE OF INTERLEUKIN-2 DURING THE ACUTE PHASE OF TRYPANOSOMA CRUZI INFECTION REVEALS ITS DOMINANT REGULATORY ROLE
Trypanosoma cruzi
Linfócitos T Reguladores
Interleucina-2
Interleucina-10
Interleucina-17
Miocardite
Trypanosoma cruzi
regulatory T cells
anti-IL-2
interleukin-2
interleukin-10
interleukin-17
myocarditis
Affilliation
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Federal University of Recôncavo da Bahia. Center of Health Sciences. Santo Antonio de Jesus, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Institute, Oswaldo Cruz. Rio de Janeiro, RJ, Brasil / University Faculties Arthur Sa Earp Neto. Petropolis Medical School. Petropolis, RJ, Brazil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Institute, Oswaldo Cruz. Rio de Janeiro, RJ, Brasil / University Faculties Arthur Sa Earp Neto. Petropolis Medical School. Petropolis, RJ, Brazil.
Abstract
Trypanosoma cruzi infection causes Chagas’ disease in humans. The infection activates
the innate and adaptative immunity in an orchestrated immune response to control
parasite growth, guaranteeing host survival. Despite an effective immune response to the
parasite in the acute phase, the infection progresses to a chronic stage. The parasite
infects different tissues such as peripheral neurons, the brain, skeletal muscle, and heart
muscle, among many others. It is evident now that tissue-specific immune responses may
develop along with anti-parasite immunity. Therefore, mechanisms to regulate immunity
and to ensure tissue-specific tolerance are operating during the infection. Studying those
immunoregulatory mechanisms is fundamental to improve host protection or control
inflammatory reactions that may lead to pathology. The role of IL-2 during T. cruzi infection
is not established. IL-2 production by T cells is strongly down-modulated early in the
disease by unknown mechanisms and remains low during the chronic phase of the
disease. IL-2 activates NK cells, CD4, and CD8 T cells and may be necessary to immunity
development. Also, the expansion and maintenance of regulatory T cells require IL-2.
Thus, IL-2 may be a key cytokine involved in promoting or down-regulating immune
responses, probably in a dose-dependent manner. This study blocked IL-2 during the
acute T. cruzi infection by using a neutralizing monoclonal antibody. The results show that
parasitemia and mortality rate was lower in animals treated with anti-IL-2. The
percentages and total numbers of CD4+CD25+Foxp3+ T cells diminished within three
weeks of infection. The numbers of splenic activated/memory CD4 and CD8 splenic T
cells increased during the acute infection. T cells producing IFN-g, TNF-a and IL-10 also
augmented in anti-IL-2-treated infected mice. The IL-2 blockade also increased the
numbers of inflammatory cells in the heart and skeletal muscles and the amount of IL-17
produced by heart T cells. These results suggest that IL-2 might be involved in the immune regulatory response during the acute T. cruzi infection, dampening T cell activation
through the expansion/maintenance of regulatory T cells and regulating IL-17
production. Therefore, the IL-2 pathway is an attractive target for therapeutic purposes
in acute and chronic phases of Chagas’ disease.
Keywords in Portuguese
Doença de ChagasTrypanosoma cruzi
Linfócitos T Reguladores
Interleucina-2
Interleucina-10
Interleucina-17
Miocardite
Keywords
Chagas’ diseaseTrypanosoma cruzi
regulatory T cells
anti-IL-2
interleukin-2
interleukin-10
interleukin-17
myocarditis
Share