Regulatory T Cells Phenotype in Different Clinical Forms of Chagas' Disease

CD25High CD4+ regulatory T cells (Treg cells) have been described as key players in immune regulation, preventing infection-induced immune pathology and limiting collateral tissue damage caused by vigorous anti-parasite immune response. In this review, we summarize data obtained by the investigation of Treg cells in different clinical forms of Chagas' disease. Ex vivo immunophenotyping of whole blood, as well as after stimulation with Trypanosoma cruzi antigens, demonstrated that individuals in the indeterminate (IND) clinical form of the disease have a higher frequency of Treg cells, suggesting that an expansion of those cells could be beneficial, possibly by limiting strong cytotoxic activity and tissue damage. Additional analysis demonstrated an activated status of Treg cells based on low expression of CD62L and high expression of CD40L, CD69, and CD54 by cells from all chagasic patients after T. cruzi antigenic stimulation. Moreover, there was an increase in the frequency of the population of Foxp3+ CD25HighCD4+ cells that was also IL-10+ in the IND group, whereas in the cardiac (CARD) group, there was an increase in the percentage of Foxp3+ CD25High CD4+ cells that expressed CTLA-4. These data suggest that IL-10 produced by Treg cells is effective in controlling disease development in IND patients. However, in CARD patients, the same regulatory mechanism, mediated by IL-10 and CTLA-4 expression is unlikely to be sufficient to control the progression of the disease. These data suggest that Treg cells may play an important role in controlling the immune response in Chagas' disease and the balance between regulatory and effector T cells may be important for the progression and development of the disease. Additional detailed analysis of the mechanisms on how these cells are activated and exert their function will certainly give insights for the rational design of procedure to achieve the appropriate balance between protection and pathology during parasite infections

Profile of Central and Effector Memory T Cells in the Progression of Chronic Human Chagas Disease

Chagas disease is a parasitic infection caused by protozoan Trypanosoma cruzi that affects approximately 11 million people in Latin America. The involvement of the host's immune response on the development of severe forms of Chagas disease has not been fully elucidated. Studies on the immune response against T. cruzi infection show that the immunoregulatory mechanisms are necessary to prevent the deleterious effect of excessive immune response stimulation and consequently the fatal outcome of the disease. A recall response against parasite antigens observed in in vitro peripheral blood cell culture clearly demonstrates that memory response is generated during infection. Memory T cells are heterogeneous and differ in both the ability to migrate and exert their effector function. This heterogeneity is reflected in the definition of central (TCM) and effector memory (TEM) T cells. Our results suggest that a balance between regulatory and effectors T cells may be important for the progression and development of the disease. Furthermore, the high percentage of central memory CD4+ T cells in indeterminate patients after stimulation suggests that these cells may modulate host's inflammatory response by controlling cell migration to tissues and their effector role during chronic phase of the disease

Avaliação de genótipos de cana-de-açúcar para início de safra na microrregião Centro de Pernambuco

As diferentes respostas dos genótipos de cana-de-açúcar (Saccharum spp.), em relação à produtividade, quando submetidos a mudanças nos diferentes ciclos de colheita, representam problema para os agricultores e grande desafio para os melhoristas, sendo de interesse comum a identificação e obtenção de variedades que apresentem como características alta produtividade agroindustrial, ampla estabilidade, longevidade e excelente viabilidade econômica em sua exploração comercial. Objetivou-se, com este trabalho, avaliar o desempenho agroindustrial de 11 clones e 15 variedades de cana-de-açúcar, na microrregião canavieira da Zona Centro de Pernambuco, considerando-se os cultivos de cana planta, soca e ressoca, e eleger os genótipos mais produtivos. O experimento foi conduzido na área agrícola da Usina Petribú, município de Lagoa de Itaenga. Utilizou-se o delineamento experimental de blocos casualizados, com quatro repetições. Foram avaliadas as variáveis toneladas de pol por hectare (TPH), toneladas de cana por hectare (TCH), fibra (FIB), pol % corrigida (PCC), pureza (PZA), teor de sólidos solúveis (BRIX) e açúcar total recuperável (ATR). Pela análise de variância, foram detectadas diferenças significativas entre os genótipos, indicando variabilidade genética. A alta estimativa da herdabilidade média para a variável TCH indicou elevada possibilidade de êxito na seleção, baseando-se neste importante componente de produção. Por meio da análise econômica, constata-se que as variedades RB92579 e RB93509 apresentam melhor desempenho para colheita no início da safra

Blood leukocytes from benznidazole-treated indeterminate chagas disease patients display an overall type-1-modulated cytokine profile upon short-term in vitro stimulation with <it>trypanosoma cruzi</it> antigens

<p>Abstract</p> <p>Background</p> <p>Benznidazole (Bz)-chemotherapy is recommended to prevent Chagas disease progression, despite its limited efficacy during chronic disease. However, the host mechanisms underlying these benefits still remain to be elucidated.</p> <p>Methods</p> <p>In this study, we have used short-term whole blood cultures to describe the cytokine profile of Bz-treated Indeterminate Chagas disease patients-(INDt) as compared to untreated patients-(IND).</p> <p>Results</p> <p>Our findings showed that IND presented increased levels of IL-10⁺neutrophils, IL-12⁺ and IL-10⁺monocytes and IFN-γ⁺NK-cells. Moreover, IND showed slight increase of IL-4⁺CD4⁺T-cells and enhanced levels of IL-10⁺CD8⁺T-cells and B-cells. Additional analysis of cytokine Low and High producers also highlighted the presence of High cytokine producers within IND, including IL-10 from CD4+ T-cells and IFN-γ from CD8⁺ T-cells, as compared to NI. The Bz-treatment lead to an overall cytokine down-regulation in the innate and adaptive compartments, including low levels of IL-12⁺ and IL-10⁺neutrophils and monocytes, IFN-γ⁺NK-cells, IL-12⁺, TNF-α⁺, IFN-γ⁺ and IL-5⁺CD4⁺T-cells and IL-10⁺B-cells, along with basal levels of cytokine-expressing CD8⁺T-cells in INDt as compared to IND. The in vitro antigen stimulation shifted the cytokine profile toward a type 1-modulated profile, with increased levels of IL-12⁺ and IL-10⁺ monocytes, IFN-γ⁺ and IL-4⁺NK-cells along with TNF-α⁺ and IFN-γ⁺CD8⁺T-cells. Analysis of Low and High cytokine producers, upon in vitro antigen stimulation, further confirm these data.</p> <p>Conclusion</p> <p>Together, our findings showed that the Bz treatment of Indeterminate Chagas’ disease patients shifts the cytokine patterns of peripheral blood monocytes, NK-cells and CD8⁺ T-cells towards a long-lasting Type-1-modulated profile that could be important to the maintenance of a non-deleterious immunological microenvironment.</p