Chronic Chagas' Disease Cardiomyopathy Patients Display an Increased IFN-γ Response to Trypanosoma cruzi Infection

Abel, L.; Rizzo, Luiz Vicente; Ianni, Bárbara Maria; Albuquerque, F; Bacal, Fernando; Carrara, Dirceu; Bocchi, Edimar Alcides; Teixeira, Henrique Couto; Mady, Charles; Kalil, Jorge; Cunha-Neto, Edécio

doi:10.1006/jaut.2001.0523

Cited by 188 publications

(223 citation statements)

References 54 publications

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“…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.…”

Section: Discussionsupporting

confidence: 87%

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

Rodrigues

Miguel

Chica

et al. 2010

Mem. Inst. Oswaldo Cruz

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The acute phase of Trypanosoma cruzi infection is associated with a strong inflammatory reaction in the heart characterised by a massive infiltration of immune cells that is dependent on the T. cruzi strain and the host response. 15d-PGJ2 belongs to a new class of anti-inflammatory compounds with possible clinical applications. We evaluated the effects of 15d-PGJ2 administered during the acute phase of T. cruzi infection in mice. Mice were infected with the Colombian strain of T. cruzi and subsequently treated with 15d-PGJ2 repeatedly for seven days. The inflammatory infiltrate was examined by histologic analysis. Slides were immunohistochemically stained to count the number and the relative size of parasite nests. Infection-induced changes in serum cytokine levels were measured by ELISA. The results demonstrated that treatment with 15d-PGJ2 reduced the inflammatory infiltrate in the skeletal muscle at the site of infection and decreased the number of lymphocytes and neutrophils in the blood. In addition, we found that 15d-PGJ2 led to a decrease in the relative volume density of amastigote nests in cardiac muscle. T. cruzi-infected animals treated with 15d-PGJ2 displayed a statistically significant increase in IL-10 levels with no change in IFN-γ levels. Taken together, we demonstrate that treatment with 15d-PGJ2 in the acute phase of Chagas disease led to a controlled immune response with decreased numbers of amastigote nests, as measured by the volume density

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Section: Discussionsupporting

confidence: 87%

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

Rodrigues

Miguel

Chica

et al. 2010

Mem. Inst. Oswaldo Cruz

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“…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.…”

Section: Discussionsupporting

confidence: 52%

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

D'avila

Guedes

Castro

et al. 2009

Mem. Inst. Oswaldo Cruz

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“…More recently, T-cell clones cross-reacting with cardiac myosin and B13 were also obtained from hearts of CChC patients (CunhaNeto et al 1996). Most of these T-cell clones are CD4 + and secrete high levels of IFN-γ (Abel et al 2001). However, there is no demonstration of a role of the response against B13 in the pathogenesis of CChC, neither in human beings, nor in experimental models.…”

Section: What Are the Mechanisms By Which T Cruzi Breaks Immunologicmentioning

confidence: 99%

The pathogenesis of Chagas' disease: when autoimmune and parasite-specific immune responses meet

Soares

Pontes-de-Carvalho

Ribeiro-dos-Santos

2001

An. Acad. Bras. Ciênc.

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Chagas' disease is a major health problem in Latin America, where it constitutes one of the leading causes of heart failure. About one fourth of Trypanosoma cruzi-infected individuals develop chronic chagasic cardiomyopathy (CChC), the most severe form of the disease. CChC is histologically characterized by the presence of multifocal inflammatory infiltrates in the heart, composed mainly by mononuclear cells, usually adhered to myocytes and leading to myocytolysis, and frequently by interstitial fibrosis. The pathogenesis of CChC is still unclear, despite intense investigations both in human beings and in animal models of the disease. Although tissue parasitism is rare in the chronic phase of infection, an immune response targeted to persistent parasites or parasite antigens is suggested, by some authors, as the pathogenic mechanism of CChC. Other researchers affirm that the lack of correlation between tissue parasitism and intensity of inflammation suggests, along with the presence of autoreactive immune responses, that CChC results from the action of an autoimmune response. Herein we review reports from the literature and our own data, which together indicate, on one hand, the participation of parasite-specific immune responses and, on the other hand, clearly demonstrate the participation of heart-specific immune responses in the pathogenesis of CChC. Moreover, multiple factors may determine whether an individual in the indeterminate form of the disease will develop CChC. The mechanisms by which T. cruzi breaks immunological tolerance to heart antigens are also discussed.

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Chronic Chagas' Disease Cardiomyopathy Patients Display an Increased IFN-γ Response to Trypanosoma cruzi Infection

Cited by 188 publications

References 54 publications

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

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

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

The pathogenesis of Chagas' disease: when autoimmune and parasite-specific immune responses meet

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