Biological behavior of different Trypanosoma cruzi isolates circulating in an endemic area for Chagas disease in the Gran Chaco region of Argentina

Abstract

The biological behavior of the different Trypanosoma cruzi strains is still unclear and the importance of exploring the relevance of these differences in natural isolates is of great significance. Herein we describe the biological behavior of four T. cruzi isolates circulating sympatrically in a restricted geographic area in Argentina endemic for Chagas Disease. These isolates were characterized as belonging to the Discrete Typing Units (DTUs) TcI, TcIII, TcV and TcVI as shown by Multilocus Enzyme Electrophoresis and Multilocus Sequence Typing. In order to study the natural behavior of the different isolates and to preserve their natural properties, we developed a vector transmission model that allows their maintenance in the laboratory. The model consisted of serial passages of these parasites between insect vectors and mice. Vector-derived parasite forms were then inoculated in C57BL/6J mice and number of parasite in peripheral blood, serological response and histological damage in acute and chronic phases of the infection were measured. Parasites from DTUs TcI, TcIII and TcVI were detected by direct fresh blood examination, while TcV parasites could only be detected by Polimerase Chain Reaction. No significant difference in the anti-T. cruzi antibody response was found during the chronic phase of infection, except for mice infected with TcV parasites where no antibodies could be detected. Histological sections showed that TcI isolate produced more damage in skeletal muscle while TcVI induced more inflammation in the heart. This work shows differential biological behavior among different parasite isolates obtained from the same cycle of transmission, permitting the opportunity to formulate future hypotheses of clinical and epidemiological importance.

Trypanosoma cruzi strains cause different myocarditis patterns in infected mice

“…A recent work reports myocarditis induced in mouse model by a single strain representative of the TcI, TcII, TcV and TcVI DTUs, concluding that a TcVI strain causes moderate myocarditis, whereas a TcV strain that did not cause cardiac inflammation exhibited almost undetectable parasite load (Ragone et al, 2012). This observation is in sharp contrast with the data in humans, where patients infected with TcV strains have been shown to suffer cardiac pathology .…”

A Monoallelic Deletion of the TcCRT Gene Increases the Attenuation of a Cultured Trypanosoma cruzi Strain, Protecting against an In Vivo Virulent Challenge

“…The percentage of metacyclic forms was recorded daily in a Neubauer chamber. In addition, we used the Tulahuén strain and a highly infective isolate recently characterized [39].…”

“…On day 15 a boost similar to the initial inoculation was administered. On day 30, antibody levels from immunized mice were determined and, on day 120, all groups were challenged with 10 4 blood trypomastigotes of a highly virulent T. cruzi TcVI isolate, recently characterized [39]. Blood was drawn from the tail tip of mice, under slight ether anesthesia using heparinized, calibrated capillary tubes.…”

Comparative study of the biological properties of Trypanosoma cruzi I genotypes in a murine experimental model

“…TcI is the DTU with the broadest distribution 74 in America, and prevalent in northern countries of South America, 75 with presence of sporadic cases in the Southern Cone (Guhl and 76 Ramírez, 2011 Also, this DTU has been associated to severe myocarditis, com-82 pared to other DTUs, as TcII, TcV and TcVI (Ramírez et al, 2010, 83 2013b; Ocaña et al, 2010;Segovia et al, 2013). By analyzing frag-84 ments of the nuclear and mitochondrial genomes of TcI, the exis-85 tence of an emerging genotype associated with human infections 86 was reported and called as TcI DOM (which previously corresponded 87 to TcIa-b/Ven DOM ) Thus, this study will determine whether or not there are significant 105 differences in the biological properties, including the assessment of 106 parasitemia, antigenicity profiles and pathological effects of TcI DOM 107 and sylvatic strains in murine biomodels (Ragone et al, 2012;Dos 108 Reis et al, 2012;Suarez et al, 2009;Rivera et al, 2000;Téllez et al, 109 2008 The weight of infected mice and negative controls were 158 recorded at intervals of 4 days using an electric balance Sartorius 159 PT-600 size 9 00 Â 7 00 Â 2 00 . Every fourth day trypomastigotes were 160 quantified by collecting 20 lL of blood from a terminal tail portion 161 in each of the infected mice using heparinized capillaries.…”