Navegando por Autor "Avelar, Renato Sathler"
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Item Are increased frequency of macrophage-like and natural killer (NK) cells, together with high levels of NK T and CD4+CD25high T cells balancing activated CD8+ T cells, the key to control Chagas'disease morbidity?.(2006) Avelar, Danielle Marchetti Vitelli; Avelar, Renato Sathler; Massara, Rodrigo Lima; Borges, Jaila Dias; Lage, Paula Souza; Lana, Marta de; Carvalho, Andréa Teixeira de; Dias, João Carlos Pinto; Santos, Silvana Maria Elói; Martins Filho, Olindo AssisThe immunological response during early human Trypanosoma cruzi infection is not completely understood, despite its role in driving the development of distinct clinical manifestations of chronic infection. Herein we report the results of a descriptive flow cytometric immunophenotyping investigation of major and minor peripheral blood leucocyte subpopulations in T. cruzi - infected children, characterizing the early stages of the indeterminate clinical form of Chagas’ disease. Our results indicated significant alterations by comparison with uninfected children, including increased values of pre-natural killer (NK)-cells (CD3 – CD16 + CD56 – ), and higher values of proinflammatory monocytes (CD14 + CD16 + HLA-DR ++ ). The higher values of activated B lymphocytes (CD19 + CD23 + ) contrasted with impaired T cell activation, indicated by lower values of CD4 + CD38 + and CD4 + HLA-DR + lymphocytes, a lower frequency of CD8 + CD38 + and CD8 + HLA-DR + cells; a decreased frequency of CD4 + CD25 HIGH regulatory T cells was also observed. These findings reinforce the hypothesis that simultaneous activation of innate and adaptive immunity mechanisms in addition to suppression of adaptive cellular immune response occur during early events of Chagas’ disease. Comparative cross-sectional analysis of these immunophenotypes with those exhibited by patients with late chronic indeterminate and cardiac forms of disease suggested that a shift toward high values of macrophage-like cells extended to basal levels of proinflammatory monocytes as well as high values of mature NK cells, NKT and regulatory T cells, may account for limited tissue damage during chronic infection favouring the establishment/maintenance of a lifelong indeterminate clinical form of the disease. On the other hand, development of an adaptive cell-mediated inflammatory immunoprofile characterized by high levels of activated CD8 + cells and basal levels of mature NK cells, NKT and CD4 + CD25 HIGH cells might lead to late chronic pathologies associated with chagasic heart disease.Item Benznidazole treatment during early indeterminate Chagas' disease shifted the cytokine expression by innate and adaptive immunity cells toward a type-1 modulated immune profile.(2006) Avelar, Renato Sathler; Avelar, Danielle Marchetti Vitelli; Massara, Rodrigo Lima; Lana, Marta de; Carvalho, Andréa Teixeira de; Dias, João Carlos Pinto; Santos, Silvana Maria Elói; Martins Filho, Olindo AssisTrypanosoma cruzi-infected children was treated with benznidazole (Bz) duringthe early-indeterminate disease (E-IND) and the cytokine pattern of innate andadaptive immune compartments were evaluated prior to the treatment and1 year after it. At first, we observed that the ex vivo cytokine profile of circula-ting leukocytes from E-IND (n ¼ 6) resembled the one observed for healthyschoolchildren (n ¼ 7). Additionally, in vitro stimulation with T. cruzi anti-gens drove the E-IND cytokine pattern toward a mixed immune profile withhigher levels of IFN-c+, TNF-a+and IL-4+NK cells, increased numbers ofIFN-c+, TNF-a+and IL-10+CD4+T cells in addition to enhanced frequencyof TNF-a+/IL-4+CD19+lymphocytes. Interestingly, upon T. cruzi antigen invitro stimulation, E-IND CD8+lymphocytes displayed a selective enhancementof IFN-c expression, accounting for a global type 1-modulated cytokine micro-environment. A shift toward a type 1-modulated profile was also the hallmarkof Bz-treated children (E-INDT). In this context, despite the mixed overall exvivo cytokine profile observed for NK and CD8+T cells, incr eased ability ofthese leukocytes to produce IFN-c in respons e to T. cruzi antigens was repor-ted. Most noteworthy was the IL-10 production evidenced at T lymphocytes,mainly CD4+cells, as well as B lymphocytes, both ex vivo and upon antigenstimulation. Toget her, these findings gave evidence that NK cells and CD8+T lymphocytes are the major sources of IFN-c, a pivotal cytokine for successfultherapeutic response in human Chagas’ disease. Moreover, our data have alsobrought additional information, pointing out IL-10 production by CD4+cellsand B lymphocytes, as the putative key element for parasite clearance in theabsence of deleterious tissue damage.Item Despite Leishvaccine and Leishmune ® trigger distinct immune profiles, their ability to activate phagocytes and CD8 + T-cells support their high-quality immunogenic potential against canine visceral leishmaniasis.(2008) Araújo, Márcio Sobreira Silva; Andrade, Renata Aline de; Vianna, Leonardo Rocha; Mayrink, Wilson; Reis, Alexandre Barbosa; Avelar, Renato Sathler; Carvalho, Andréa Teixeira de; Andrade, Mariléia Chaves; Melo, Maria Norma; Martins Filho, Olindo AssisPhenotypic features of peripheral blood leukocytes have been investigated as a prerequisite to characterize the protective immunity attributed to both Leishvaccine and Leishmune ® . Our results showed that either those vaccine were accompanied by distinct profiles on innate immune compartment. While Leishvaccine promoted early changes in phenotypic fea-tures of neutrophils and eosinophils with late involvement of monocytes, Leishmune ® induced early and persistent activation of neutrophils and monocytes, without changes on eosinophil activation status. Regarding the adaptive immunity, Leishvaccine sponsored a mixed profile, associated with phenotypic changes of T and B-lymphocytes. Major phenotypic changes in CD4 + T-cells with transient activation of CD8 + T-cell, besides decreased frequency of B-cell expressingItem Etiological treatment during early chronic indeterminate Chagas disease incites an activated status on innate and adaptive immunity associated with a type 1-modulated cytokine pattern.(2008) Avelar, Renato Sathler; Avelar, Danielle Marchetti Vitelli; Massara, Rodrigo Lima; Lana, Marta de; Dias, João Carlos Pinto; Carvalho, Andréa Teixeira de; Santos, Silvana Maria Elói; Martins Filho, Olindo AssisPro-inflammatory immune response is usually associated with Chagas disease pathogenesis, but is also relevant to treatment effectiveness. Cross-sectional studies have suggested that this activated state may persist for years after therapeutic intervention. However, short-term longitudinal investigation has suggested that the Benznidazole treatment (Bz-treatment) leads to decreased immunological activation. In order to elucidate this issue, we performed a longitudinal study to evaluate the immunological status following Bz-treatment during early indeterminate Chagas disease. Our results demonstrated that Bz-treatment led to higher activation status of circulating monocytes but was negatively associated with the number of IL-12þCD14þ cells. Moreover, Bz-treatment triggered a high frequency of circulating CD3_CD16þCD56_ NK cells, in addition to elevated activation status associated with a type 1-modulated cytokine pattern. Bz-treatment induced substantial T and B-cell activation status associated with an overall IL-10 modulated type 1 cytokine profile. In summary, these findings provide new information regarding immune activation status following the etiological treatment of Chagas disease. These results suggest that in addition to the increased number of activated leukocytes in the peripheral blood, Bz-treatment may also involve a qualitative change in their functional capacity that drives their activation state toward a modulated cytokine profile. These changes may account for the benefits of etiological treatment of Chagas disease.Item Immunological changes in canine peripheral blood leukocytes triggered by immunization with first or second generation vaccines against canine visceral leishmaniasis.(2011) Araújo, Márcio Sobreira Silva; Andrade, Renata Aline de; Avelar, Renato Sathler; Magalhães, Camila Paula; Carvalho, Andréa Teixeira de; Andrade, Mariléia Chaves; Campolina, Sabrina Sidney; Melo, Maria Norma; Vianna, Leonardo Rocha; Mayrink, Wilson; Reis, Alexandre Barbosa; Malaquias, Luiz Cosme Cotta; Rocha, Luciana Morais; Martins Filho, Olindo AssisIn this study, we summarized the major phenotypic/functional aspects of circulating leuko-cytes following canine immunization with Leishvaccine and Leishmune ®. Our findings showed that Leishvaccine triggered early changes in the innate immunity (neutrophils and eosinophils) with late alterations on monocytes. Conversely, Leishmune ® induced early phenotypic changes in both, neutrophils and monocytes. Moreover, Leishvaccine triggered mixed activation-related phenotypic changes on T-cells (CD4 + and CD8 +) and B-lymphocytes, hereas Leishmune® promoted a selective response, mainly associated with CD8 + T-cell activation. Mixed cytokine profile (IFN- /IL-4) was observed in Leishvaccine immunized dogs whereas a selective pro-inflammatory pattern (IFN- /NO) was induced by Leishmune ® vaccination. The distinct immunological profile triggered by Leishvaccine and Leishmune ® may be a direct consequence of the distinct biochemical composition of these immunobiological, i.e. complex versus purified Leishmaniaantigen along with Bacillus Calmette-Guérin (BCG) versus saponin adjuvant. Both immunobiologicals are able to acti-vate phagocytes and CD8 + T-cells and therefore could be considered as a putative vaccines against canine visceral leishmaniasis (CVL)Item T-cell-derived cytokines, nitric oxide production by peripheral blood monocytes and seric anti- Leishmania (Leishmania) chagasi IgG subclass patterns following immunization against canine visceral leishmaniasis using Leishvaccine and Leishmune ®.(2009) Araújo, Márcio Sobreira Silva; Andrade, Renata Aline de; Avelar, Renato Sathler; Carvalho, Andréa Teixeira de; Andrade, Mariléia Chaves; Vianna, Leonardo Rocha; Mayrink, Wilson; Reis, Alexandre Barbosa; Malaquias, Luiz Cosme Cotta; Melo, Maria Norma; Martins Filho, Olindo AssisIt is generally accepted that distinct cytokine expression by the cellular immune response plays a critica role during the outcome of experimental as well as natural canine visceral Leishmaniasis (CVL). Despite the fact that immunoprophylaxis of CVL has become an important control strategy and protective immunity has been reported upon immunization with whole as well as purifiedLeishmaniaantigens, the cytokine profile of T-cells triggered by anti-CVL vaccines still remain to be determined. Herein, we have developed a cross-sectional analysis of German Shepherd dogs submitted to vaccination protocols with Leishvaccine (n = 6) and Leishmune ® (n = 6). Our data identified distinct immunological profiles elicited by Leishvaccine and Leishmune ® , with the Leishvaccine triggering a mixed, IFN- and IL-4, cytokine pattern in addition to high levels of anti- LeishmaniaIgG1, whereas the Leishmune ® induced an immunological pattern char- acterized by enhanced levels of IFN- , NO and anti- Leishmania chagasi IgG2. It was important to notice that despite the distinct immunological patterns triggered by Leishvaccine and Leishmune ® , the ability of both immunobiologicals to activate T-cell-derived IFN- synthesis further suggesting their immunogenic potential against CVL. These findings added support to our hypothesis that both antigenic composition (whole antigen in Leishvaccine versus purified antigen in Leishmune ® ) as well as the adjuvant nature (BGC and saponin) used for the vaccine formulation may count for the distinct activation pattern observed.