The role of the immune response on the development of severe clinical forms of human Chagas disease

Corrêa-Oliveira, Rodrigo; Gomes, Juliana de Assis Silva; Lemos, Elenice Moreira; Cardoso, Glenda Meira; Reis, Débora d’Ávila; Adad, Sheila Jorge; Crema, Eduardo; Martins‐Filho, Olindo Assis; Costa, Manoel Otávio Rocha; Gazzinelli, Giovanni; Bahia-Oliveira, Lilian M. G.

doi:10.1590/s0074-02761999000700042

Cited by 47 publications

(54 citation statements)

References 14 publications

(10 reference statements)

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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%

“…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).…”

mentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 52%

mentioning

confidence: 99%

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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“…In human patients' cardiac biopsies, among the mononuclear cells, macrophages and CD8 + T cells represent the majority of the infi ltrate (Higuchi et al 1997). IFN-γ can be detected in tissues via in situ immunohistochemistry (Bahia-Oliveira et al 1998, Correa-Oliveira et al 1999) and appears to be correlated with the presence of CD8 + T cells (Higuchi et al 1997, Reis et al 1997). In addition, T. cruzispecifi c human CTL have been identifi ed (Thomson et al 1998, Wizel et al 1998.…”

Section: Human Studiesmentioning

confidence: 99%

An overview of chagasic cardiomyopathy: pathogenic importance of oxidative stress

Zacks

Wen

Vyatkina

et al. 2005

An. Acad. Bras. Ciênc.

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There is growing evidence to suggest that chagasic myocardia are exposed to sustained oxidative stressinduced injuries that may contribute to disease progression. Pathogen invasion-and replication-mediated cellular injuries and immune-mediated cytotoxic reactions are the common source of reactive oxygen species (ROS) in infectious etiologies. However, our understanding of the source and role of oxidative stress in chagasic cardiomyopathy (CCM) remains incomplete. In this review, we discuss the evidence for increased oxidative stress in chagasic disease, with emphasis on mitochondrial abnormalities, electron transport chain dysfunction and its role in sustaining oxidative stress in myocardium. We discuss the literature reporting the consequences of sustained oxidative stress in CCM pathogenesis.Key words: chagasic cardiomyopathy, reactive oxygen species, inflammation, mitochondria, oxidant/antioxidant status, oxidative damage. PARASITE, VECTOR AND TRANSMISSIONTrypanosoma cruzi, a parasitic protozoan of the ancient branch of eukaryotes (Kingdom Eukaryota, Order Kinetoplastida), is the etiological agent of Chagas disease in humans (Miles 2003). Currently, the World Health Organization estimates that 11-18 million individuals are infected worldwide (WHO 2002). Transmission of T. cruzi occurs predominantly via insect vectors of the subfamily Triatoma, family Reduviidae, referred to as " kissing bugs". Residing in the peridomestic habitat of mud-thatch Correspondence to: Nisha Garg Ph.D. E-mail: nigarg@utmb.edu houses in rural areas (Mott et al. 1978), Triatoma infestans in South America, Rhodnius prolixus in Venezuela, Colombia and Central America (Schofi eld and Dias 1999), and Triatoma barberi in Mexico (Guzman 2001), are the most common species responsible for transmission. Improvements in housing conditions and vector control measures instituted by the Southern Cone Initiative in 1991 have contributed to a decline in transmission in endemic countries (Schofi eld and Dias 1999). However, concern remains that reinfestation of homes by secondary sylvatic vectors, e.g. Triatoma sordida, will compromise the long-term effi cacy of vector control measures in Brazil and other Southern American countries (Monteiro et al. 2001, WHO 2002. Blood transfusion and organ transplantation represent further routes of T. cruzi transmission. Although many countries in Latin America screen blood donations for T. cruzi, infection rates ranging from 0.1% to 24.4% are estimated to occur through transfusion (WHO 2002).In the U.S., vector-transmitted human infections have been reported in the southern States (Ochs et al. 1996, Herwaldt et al. 2000. Several studies have shown the presence of the insect vector as well as infection of domestic dogs and wild animals in the US (Meurs et al. 1998, Bradley et al. 2000, Beard et al. 2003, Yabsley and Noblet 2002. Further, due to signifi cant increases in immigration to the USA and Canada from endemic countries and perinatal transmission, it is estimated that ∼ 100, 000 people residing...

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“…It was particularly surprising that, even at the acute stage (30 dpi), IFN-␥ production by splenocytes ϩ T cells, the dominant resident immune cells in the heart, have a toxic effect on the host, as many of the CD8 ϩ T cells express granzyme A, which results in nonspecific bystander cell death and tissue necrosis (27). Others have shown that the frequency of IFN-␥-producing T cells specific for T. cruzi correlate with the severity of chronic disease in chagasic humans and experimental animals (7,33). Circulating levels of IFN-␥ and its production by peripheral blood mononuclear cells stimulated in vitro with T. cruzi antigen have been implicated as risk factors in identifying asymptomatic, seropositive patients at risk of developing symptomatic chronic cardiomyopathy (7).…”

Section: Discussionmentioning

confidence: 99%

“…Others have shown that the frequency of IFN-␥-producing T cells specific for T. cruzi correlate with the severity of chronic disease in chagasic humans and experimental animals (7,33). Circulating levels of IFN-␥ and its production by peripheral blood mononuclear cells stimulated in vitro with T. cruzi antigen have been implicated as risk factors in identifying asymptomatic, seropositive patients at risk of developing symptomatic chronic cardiomyopathy (7). In this study, we indeed observed, irrespective of vaccination status, a substantially high infiltration of mononuclear cells in the heart and skeletal muscle in response to a challenge infection with T. cruzi.…”

Section: Discussionmentioning

confidence: 99%

Previously Unrecognized Vaccine Candidates ControlTrypanosoma cruziInfection and Immunopathology in Mice

Bhatia

Garg

2008

Clin Vaccine Immunol

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Trypanosoma cruzi is the etiologic agent of Chagas' disease, a major health problem in Latin America and an emerging infectious disease in the United States. Previously, we screened a T. cruzi sequence database by a computational-bioinformatic approach and identified antigens that exhibited the characteristics of good vaccine candidates. In this study, we tested the vaccine efficacy of three of the putative candidate antigens against T. cruzi infection and disease in a mouse model. C57BL/6 mice vaccinated with T. cruzi G1 (TcG1)-, TcG2-, or TcG4-encoding plasmids and cytokine (interleukin-12 and granulocyte-macrophage colony-stimulating factor) expression plasmids elicited a strong Th1-type antibody response dominated by immunoglobulin G2b (IgG2b)/IgG1 isotypes. The dominant IgG2b/IgG1 antibody response was maintained after a challenge infection and was associated with 50 to 90% control of the acute-phase tissue parasite burden and an almost undetectable level of tissue parasites during the chronic phase, as determined by a sensitive T. cruzi 18S rRNA gene-specific real-time PCR approach. Splenocytes from vaccinated-and-infected mice, compared to unvaccinated-and-infected mice, exhibited decreased (ϳ50% lower) proliferation and gamma interferon (IFN-␥) production when stimulated in vitro with T. cruzi antigens, thus suggesting that protection from challenge infection was not provided by an active T-cell response. Subsequently, the serum and cardiac levels of IFN-␥ and tumor necrosis factor alpha and infiltration of inflammatory infiltrate in the heart were decreased in vaccinated mice during the course of infection and chronic disease development. Taken together, these results demonstrate the identification of novel vaccine candidates that provided protection from T. cruzi-induced immunopathology in experimental mice.

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The role of the immune response on the development of severe clinical forms of human Chagas disease

Cited by 47 publications

References 14 publications

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

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

An overview of chagasic cardiomyopathy: pathogenic importance of oxidative stress

Previously Unrecognized Vaccine Candidates ControlTrypanosoma cruziInfection and Immunopathology in Mice

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