Chagasic patients develop a type 1 immune response to Trypanosoma cruzi trans‐sialidase

Abstract

Infective forms of Trypanosoma cruzi, the parasite that causes Chagas' disease, express on their surface an enzyme denominated trans-sialidase (TS). The present study was designed to evaluate the naturally acquired immune responses to a bacterial recombinant protein representing the catalytic domain of TS in chronically infected chagasic individuals. The cellular immune response was measured by in-vitro T-cell proliferation and by interferon (INF)-gamma, interleukin (IL)-4 and IL-10 production in response to a whole-parasite homogenate and the recombinant protein. The peripheral blood mononuclear cells of 78.6% of 28 chagasic patients responded to the recombinant protein as estimated by T-cell proliferation. With respect to cytokine production, 88% of the cells of the chagasic individuals produced IFN-gamma on stimulation with the recombinant protein. In contrast, IL-4 or IL-10 were minimally produced in response to TS. The cellular immune response was specific because most healthy individuals never exposed to T. cruzi failed to react with this recombinant protein. The plasma of 71.4% or 100% of chagasic patients had IgG antibodies as determined by ELISA or by the presence of TS inhibitory antibodies, respectively. We conclude that the catalytic domain of TS is recognized by IFN-gamma producing type 1 cells and antibodies in a large proportion of patients infected with T. cruzi.

15d-PGJ2 modulates acute immune responses to Trypanosoma cruzi infection

“…These results are consistent with a modulatory type of immune response (Ribeirao et al 2000, Abel et al 2001). Importantly, a recent study demonstrated a biased distribution of high IL-10 expression amongst indeterminate chagasic patients.…”

Immunological imbalance between IFN-³ and IL-10 levels in the sera of patients with the cardiac form of Chagas disease

“…These results were confirmed by other studies, which also showed that, although the levels of TNF-α and NO were higher in sera from chagasic patients, compared to non-chagasic individuals, no difference was observed between asymptomatic and symptomatic chagasic patients (Perez-Fuentes et al 2008). IFN-γ levels were similar in the sera of asymptomatic individuals and CARD patients that presented the form of the disease (Ribeirao et al 2000). Thus, the findings of several studies have failed to clearly establish a correlation between the concentration of circulating cytokines and the cardiac form of Chagas disease.…”

“…Although the present results showed no differences between IL-10 and IFN-γ levels in CARD and IND patients, the IND patients displayed a positive correlation between inflammatory and regulatory cytokine production, indicating a controlled immune response. These findings are supported by the higher production of IFN-γ and TNF-α associated with high IL-10 levels described in IND patients, while CARD patients showed an unregulated Th1 response (Bahia-Oliveira et al 1998, Correa-Oliveira et al 1999, Ribeirao et al 2000, Abel et al 2001, Gomes et al 2005. A lack of co-regulation between inflammatory and anti-inflammatory cytokines associated with severe disease was also demonstrated in human patients with leishmaniasis (Gaze et al 2006), strengthening this hypothesis.…”

“…Antibody production and T-cell responses have been studied in patients with Chagas disease (Morgan et al 1996, Cordeiro et al 2001) and experimental models (Giordanengo et al 2000, Guedes et al 2008. Mononuclear cells from the heart tissue or peripheral blood of patients with the cardiac form of the disease produce higher IFN-γ and TNF-α and lower or absent production of IL-10 and IL-4 compared with asymptomatic individuals (Correa-Oliveira et al 1999, Ribeirao et al 2000, Gomes et al 2003. However, other studies have shown that the mean levels of mRNA expression for IL-5, IL-10, IL-13 and IFN-γ were dramatically increased in peripheral blood mononuclear cells (PBMCs) freshly isolated from chagasic patients, regardless of the clinical form, compared to uninfected individuals (NI) (Dutra et al 1997).…”

Immunological and non-immunological effects of cytokines and chemokines in the pathogenesis of chronic Chagas disease cardiomyopathy

“…Mononuclear cells increase their cytokine production, leading to increased plasma levels of TNF-α and IFN-γ, and are even detected in infected individuals with indeterminate forms of Chagas disease (Ribeirão et al 2000, Abel et al 2001, Ferreira et al 2003, Talvani et al 2004, which is probably in response to parasite persistent. The subset of patients that develop Chagas cardiomyopathy displays an array of immunological alterations consistent with an exacerbated Th1 immune response.…”