Acta Tropica 167 (2017) 40–49
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Acta Tropica
jo u r n al homep age: www.elsevier.com/locate/actatropica
Myocarditis in different experimental models infected by
Trypanosoma cruzi is correlated with the production of IgG1 isotype
Ivo Santana Caldas
a,b,∗
, Livia de Figueiredo Diniz
b
, Paulo Marcos da Matta Guedes
c
,
Álvaro Fernando da Silva do Nascimento
a
, Lúcia Maria da Cunha Galvão
d
,
Wanderson Geraldo de Lima
a
, Sérgio Caldas
e
, Maria Terezinha Bahia
a
a
Laboratório de Doenc ¸ as Parasitárias, Escola de Medicina, Departamento de Ciências Biológicas & Núcleo de Pesquisas em Ciências Biológicas,
Universidade Federal de Ouro Preto, Campus Universitário, Morro do Cruzeiro, Ouro Preto, MG, Brazil
b
Instituto de Ciências Biomédicas, Departamento de Patologia e Parasitologia Básica, Universidade Federal de Alfenas, Alfenas, MG, 37130-001, Brazil
c
Departamento de Microbiologia e Parasitologia, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil
d
Departamento de Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
e
Fundac ¸ ão Ezequiel Dias, Rua Conde Pereira Carneiro, 80, Gameleira, Belo Horizonte, Minas Gerais, Brazil
a r t i c l e i n f o
Article history:
Received 16 September 2016
Received in revised form 4 December 2016
Accepted 15 December 2016
Available online 16 December 2016
Keywords:
Trypanosoma cruzi
Chagas disease
Immunopathogenesis
IgG1
Myocarditis
a b s t r a c t
This study was designed to verify the relationship between IgG antibodies isotypes and myocarditis in
Trypanosoma cruzi infection using mice and dogs infected with different T. cruzi strains. The animals were
infected with benznidazole-susceptible Berenice-78 and benznidazole-resistant AAS and VL-10 strains.
The IgG subtypes were measured in serum samples from dogs (IgG, IgG1, and IgG2) and mice (IgG, IgG1,
IgG2a, and IgG2b). The infection of dogs with VL-10 strain induced the highest levels of heart inflammation
while intermediate and lower levels were detected with Berenice-78 and AAS strains, respectively. Similar
results were found in mice infected with VL-10, but not in those infected with AAS or Berenice-78 strains.
The AAS strain induced higher levels of heart inflammation in mice, while Berenice-78 strain was not
able to induce it. Correlation analysis between myocarditis and antibody reactivity index revealed very
interesting results, mainly for IgG and IgG1, the latter being the most exciting. High IgG1 showed a
significant correlation with myocarditis in both experimental models, being more significant in dogs
(r = 0.94, p < 0.0001) than in mice (r = 0.58, p = 0.047). Overall, our data suggest that IgG1 could be a good
marker to demonstrate myocarditis intensity in Chagas disease.
© 2016 Elsevier B.V. All rights reserved.
1. Introduction
Chagas disease remains one of the major social problems in
Latin America, affecting around 6 million people worldwide. It
is estimated that approximately 70 million people are at risk of
acquiring the disease (WHO, 2016). The parasitic infection is a
chronic, disabling, and debilitating disease, having an important
socio-economic and cultural impact. Symptomatic manifestations
are found in 20–30% of infected individuals, most of them related
with intestinal and cardiac alterations, with Chagas heart dis-
ease being the main cause of death associated with the disease
(Prata, 2001). Several factors generated in response to the parasite
∗
Corresponding author at: Laboratório de Doenc ¸ as Parasitárias, Núcleo de
Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto, Ouro Preto,
MG, 35400-000, Brazil.
E-mail address: ivo.caldas@unifal-mg.edu.br (I.S. Caldas).
infection have importance in the pathogenesis of Chagas disease,
and the balance between pro-inflammatory and anti-inflammatory
cytokines appears to be critical in the development of the chronic
phase of the infection (Guedes et al., 2009). In this line, the host
immune response plays a crucial role in host resistance to infec-
tion, but can also lead to tissue damage genesis (Andrade et al.,
2014).
Cardiac involvement is the most serious manifestation of Chagas
disease and one of the leading causes of mortality in Latin Amer-
ica (Prata et al., 1986). Chagasic cardiomyopathy has a progressive
fibrosing character, this progressive condition being closely associ-
ated with the increased inflammatory events involving the cardiac
infected organ. A direct destruction of cardiomyocytes has been
observed in these inflammatory processes, resulting in clinical
cases with conductivity changes, rhythmic variations, and impaired
myocardial contractility (Andrade et al., 1997). Understanding the
key mechanisms involved in cardiomyocyte destruction and the
identification of cardiac damage markers in Chagas’ disease could
http://dx.doi.org/10.1016/j.actatropica.2016.12.015
0001-706X/© 2016 Elsevier B.V. All rights reserved.