Alternative Th17 and CD4+ CD25+ FoxP3+ cell frequencies increase and correlate with worse cardiac function in Chagas cardiomyopathy.

Immune homeostasis has been suggested to play an important role in the clinical evolution of chronic Chagas disease; however, the immunopathologic factors involved have not been fully elucidated. Therefore, our study aimed to analyse the frequency of CD4+ CD25+ FoxP3+ cells, classic Th17 cells, alternative Th17 cells and IL-17+ B cells from peripheral blood of chronic cardiac patients after in vitro stimulation with Trypanosoma cruzi soluble EPI antigen. Patients were selected and classified according to clinical evaluation of cardiac involvement: mild, B1 (CARD1) (n = 20) and severe, C (CARD2) (n = 11). Patients with the indeterminate form of CD were included as the control group A (IND) (n = 17). Blood samples were collected and cultured in the presence of EPI antigen. Cells frequency and median fluorescence intensity (MFI) were obtained by flow cytometry. Our results showed that only CD4+ CD25+ FoxP3+ , CD4+ CD25high FoxP3+ , CD4+ IL-17+ IFN-γ- and CD4+ IL-17+ IFN-γ+ cells are more frequent in patients with severe cardiac disease and correlate with worse global cardiac function. However, while indeterminate patients demonstrated a positive correlation between CD4+ CD25+ FoxP3+ and CD4+ IL-17+ IFN-γ- Th17 cells, this relationship was not observed in cardiac patients. IL-17 expression by Th17 cells and B cells correlated with disease progression. Altogether our results suggest that the clinical progression of Chagas cardiomyopathy involves worsening of inflammation and impairment of immunoregulatory mechanisms.

Immunomodulation of allergic response in children and adolescents: What we can learn from lymphatic filarial infection.

BACKGROUND: Although it is well known that allergic diseases involve a strong Th2 immune response, with production of high levels of specific IgE allergen, knowledge on the association between filarial infection and allergies, among paediatric patients is scarce. OBJECTIVE: To evaluate the allergic response patterns in cases of filarial infection by comparing peripheral eosinophils, total IgE levels, immediate hypersensitivity and cytokine levels in children and adolescents in Brazil. METHODS: This was an exploratory study with three groups: (I) with filarial infection and without allergic diseases; (II) without filarial infection and with allergic diseases; and (III) without filarial infection and without allergic diseases. The prick test and specific IgE tests for aeroallergens were performed using five antigens. Peripheral eosinophils and total IgE were also evaluated. IL-4 and IL-5 were determined using whole-blood culture stimulated by three antigens. RESULTS: Eosinophilia and elevated levels of total IgE (≥400IU/dl) were observed in all groups. The prick test was positive in 56.6% of the cases. Group I presented hypersensitive responses similar to the allergic disease groups. In the whole-blood culture stimulated by Dermatophagoides pteronyssinus, average IL-4 production did not differ significantly among the groups, but IL5 production resulting from stimulation was greater in the allergic disease groups (p<0.05). CONCLUSIONS: The allergic response pattern in group with filarial infection was similar to that of the groups with and without allergic diseases, but the response to IL-5 in the culture stimulated by D. pteronyssinus was an exclusive characteristic of the allergic group.

Receptor Antagonist of IL-13 Exerts a Potential Negative Regulation During Early Infection of Human Schistosomiasis.

The pathology of schistosomiasis is associated with the formation of granulomas, and this process is associated with liver fibrosis. Studies indicate that Th1 cytokines reduce fibrosis in schistosomiasis, while Th2 cytokines play a part in the progression of fibrosis, and IL-13 has a critical role in this process. The IL-13Rα2 receptor, known as a 'receptor antagonist' binds with high affinity to IL-13, and studies have identified that this plays a part in reducing fibrosis and the size of granulomas. The objective of this study was to evaluate the function of IL-13Rα2 and cellular immune response in hepatic fibrosis. A negative correlation between IL-13Rα2 and IL-13 was found, suggesting an increase in cytokine in early fibrosis. Initially, a negative correlation between IFN-γ and IL-13 was found in patients without fibrosis, and subsequently, this correlation was found to be positive in patients with severe fibrosis, thereby highlighting a new mechanism for regulating the progress of periportal fibrosis. There was a positive correlation between the profiles of Th1 and Th2 cytokines, suggesting the presence of both responses, thus regulating the disease. The results contribute to a better understanding of the immune mechanisms that control the process of hepatic fibrogenesis in schistosomiasis in humans.

Interleukin-10 and tumour necrosis factor-alpha serum levels in chronic Chagas disease patients.

In Chagas disease, chronically infected individuals may be asymptomatic or may present cardiac or digestive complications, and it is well known that the human immune response is related to different clinical manifestations. Different patterns of cytokine levels have been previously described in different clinical forms of this disease, but contradictory results are reported. Our aim was to evaluate the serum levels of interleukin-10 and tumour necrosis factor-alpha in patients with asymptomatic and cardiac Chagas disease. The serum interleukin-10 levels in patients with cardiomyopathy were higher than those in asymptomatic patients, mainly in those without heart enlargement. Although no significant difference was observed in serum tumour necrosis factor-alpha levels among the patients, we found that cardiac patients also present high levels of this cytokine, largely those with heart dilatation. Therefore, these cytokines play an important role in chronic Chagas disease cardiomyopathy. Follow-up investigations of these and other cytokines in patients with chronic Chagas disease need to be conducted to improve the understanding of the immunopathology of this disease.

Cytokine levels in serious cardiopathy of Chagas disease after in vitro stimulation with recombinant antigens from Trypanosoma cruzi.

The clinical manifestations of human Chagas disease are associated with distinct and complex host-parasite interactions that directly involve the host's immune system. In this study, we analysed the relationship between the production of intracytoplasmic cytokines after in vitro stimulation with the recombinant antigens CRA (cytoplasmatic repetitive antigen) or FRA (flagellar repetitive antigen) from Trypanosoma cruzi and the chronic cardiac or indeterminate clinical forms of Chagas disease. The chagasic patient groups consisted of 39 individuals, selected at the Chagas Disease Unit of the Oswaldo Cruz University Hospital, whom presented either a cardiac form without cardiac dilatation (CARD 1), cardiac form with cardiac dilatation (CARD 2) or indeterminate form (IND). Blood samples were obtained from these patients and cultured in the presence of CRA or FRA. The cytokines produced by lymphocytes and monocytes after antigen stimulation were analysed by flow cytometry. Our results showed that the IFN-γ and TNF-α, produced by CD8+ T lymphocytes after in vitro stimulation with CRA, differed among chagasic patients with CARD 1, CARD 2 or IND. We propose that these cytokines could be utilized as immunological markers for clinical cardiac forms of Chagas disease. In a prospective study of patients presenting IND and CARD 1, the assay performed in this paper could serve as a tool to monitor therapeutic interventions, thus improving the patient's quality of life.