Browsing by Author "Massara, Rodrigo Lima"

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    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 Assis
    The 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.
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    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 Assis
    Trypanosoma 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.
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    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 Assis
    Pro-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.
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    Using a multistate occupancy approach to determine molecular diagnostic accuracy and factors afecting avian haemosporidian infections.
    (2020) Rodrigues, Raquel Andrade; Massara, Rodrigo Lima; Bailey, Larissa L.; Pichorim, Mauro; Moreira, Patrícia de Abreu; Braga, Erika Martins
    The use of a sensitive and accurate parasite detection methodology is crucial in studies exploring prevalence of parasites in host populations or communities, and uncertainty in identifying parasite genera and/or lineages may limit the understanding of host-parasite interactions. Here, we used a multistate occupancy approach that accounts for imperfect detection to assess whether sex and breeding season influenced the prevalence of a specific Haemoproteus lineage (TARUF02) in a white-lined tanager population. Likewise, we explored whether the probability of detecting the target parasite in an infected bird using PCR and sequencing analyses may be influenced by season and host sex. We found little evidence that sex influenced the probability of an individual host being infected by a haemosporidian parasite. Conversely, we found that the probability of infection by Haemoproteus TARUF02 was ~30% higher during the breeding season, reflecting a higher prevalence of this parasite in this season. The probability that PCR detects DNA of haemosporidian parasite was higher for female birds, suggesting that they are more prone to be parasitized with parasitemia levels that are more successfully detected by molecular analysis. Sequencing successfully determined the Haemoproteus TARUF02 lineage in 60% of samples collected during the breeding season and 84% of samples collected during the non-breeding season. Understanding the ecology of hosts and aspects of their physiology that may influence the parasite infection is essential to better understanding of hemoparasite infections and how parasites influence their native hosts, through decreasing reproductive success, lifespan, and/or survival.