Short communication
IgG isotype profile is correlated with cardiomegaly in Beagle dogs infected with distinct Trypanosoma cruzi strains

https://doi.org/10.1016/j.vetimm.2008.03.003Get rights and content

Abstract

A systematic study following infection by various strains of the protozoan parasite, Trypanosoma cruzi, and the simultaneous monitoring of the humoral immune response together with the elicited cellular response, could add greatly to our understanding of differences between strains of this important human pathogen. In that sense, acute and chronic infections with distinct T. cruzi strains (Y, Berenice-78 and ABC) in Beagle dogs were studied through a longitudinal evaluation of immunoglobulin G (IgG), IgG1 and IgG2 isotypes (by ELISA and flow cytometry (FC)), as well as measurements of peripheral blood mononuclear cell (PBMC) proliferation over a 100-week period, and their correlation with cardiomegaly. Our results show that infected animals presenting cardiomegaly showed lower or absent levels of IgG1 during the chronic phase of the infection, when compared to those that did not show an increase in heart weight. In that manner, our results suggest that IgG1 could be used as a marker for cardiac pathogenicity in Chagas disease.

Introduction

Chagas disease is endemic from Mexico to Argentina, where it is estimated that 13 million people are infected with Trypanosoma cruzi in the Central and South America, and 75 million present a potential risk of infection (WHO, 2005). During chronic phase of infection, the majority of chagasic patients (about 70%) do not present clinical signs (indeterminate form), however, about 10–20% develop a digestive (megaesophagus and megacolon) and cardiac form of disease, respectively (Tafuri, 1987). The immunopathological mechanisms involved in the pathogenesis of chagasic cardiomyopathy are not completely elucidated. The profile of inflammatory cells, as well as production of cytokines, chemokines, antibodies and soluble factors that act in cellular signaling may be the key for a better comprehension of chronic lesions genesis, determining why some patients demonstrate cardiac manifestations and another remain with the indeterminate form of Chagas disease.

A major set back in research efforts to elucidate the pathogenesis mechanisms of chronic Chagas’ disease is the lack of a suitable animal model. The canine model reproduces diffused chronic myocarditis and has shown the cardiac, pathological and electrocardiographic changes also seen in humans (Lana et al., 1992, Guedes et al., 2007). Moreover, recent findings demonstrated that the dog is a good model for chemotherapy studies in Chagas’ disease (Guedes et al., 2002). The aim of this study is to evaluate the kinetics of IgG1 and IgG2 isotypes production and proliferation of peripheral blood mononuclear cells (PBMC) against parasite antigens, correlating the data to cardiomegaly found in Beagle dogs infected with Y, Berenice-78 and ABC T. cruzi strains.

Section snippets

T. cruzi strains

In this study, three distinct strains were used. The Y T. cruzi strain isolated from an acute human case (Silva and Nussenzweig, 1953); Berenice-78, isolated by xenoculture (the technique consist in putting nymphs of not infected haematophagus triatomines insect to feed in a patient and culture is performed with intestinal contents and parasites isolated) in 1978 from what was considered the first clinical case of the disease in Brazil, in a patient with the indeterminate form of the disease (

Results and discussion

We initially evaluated the establishment of humoral response kinetics during the acute phase of the disease. We observed the same profile of total IgG and IgG2, both by ELISA and FC, in the animals infected with the three T. cruzi strains. However, different IgG1 profiles were observed by ELISA and FC (Fig. 1). The distinct production of IgG subclasses by ELISA and FC was described for human patients of different geographical areas (Cerban et al., 1993, Morgan et al., 1996, Cordeiro et al., 2001

Acknowledgments

This work was supported by Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG), Conselho Nacional de Pesquisa de Desenvolvimento Científico e Tecnológico (CNPq), and research fellowships from CNPq (Galvão, L.M.C., Afonso, L.C.C., Lana, M., Bahia, M.T., and Guedes, P.M.M. received doctoral fellowships). We also thank Lívia de Figueiredo and Geovam Crepalde from the Laboratório de Doença de Chagas, Instituto de Ciências Biológicas, UFOP, for animal care and Afonso da Costa Viana

References (26)

  • P. Deplazes et al.

    Specific IgG1 and IgG2 antibody responses of dogs to Leishmania infantum and other parasites

    Paras. Immunol.

    (1995)
  • L. Giordanengo et al.

    Cruzipain induces autoimmune response against skeletal muscle and tissue damage in mice

    Muscle Nerve.

    (2000)
  • J.A. Gomes et al.

    Evidence that development of severe cardiomyopathy in human Chagas’ disease is due to a Th1-specific immune response

    Infect. Immun.

    (2003)
  • Cited by (20)

    • Trypanosomiasis

      2022, Greene's Infectious Diseases of the Dog and Cat, Fifth Edition
    • Myocarditis in different experimental models infected by Trypanosoma cruzi is correlated with the production of IgG1 isotype

      2017, Acta Tropica
      Citation Excerpt :

      Lytic activity of specific antibodies in human disease has also been demonstrated, in this case, the IgG1 antibody (Cordeiro et al., 2001). Other authors, using a dog as the experimental model, have shown the negative relationship between the severity of the disease and IgG1 levels (Guedes et al., 2008). Deplazes et al. (1995) showed that antibody-mediated response is stimulated by different cytokines and that in symptomatic or asymptomatic infections are associated with the differential production of IgG1 or IgG2.

    View all citing articles on Scopus
    View full text