Relationships between histopathological findings and phylogenetic divergence in Trypanosoma cruzi

Abstract

SummaryProblems have been raised by natural genetic diversity of Trypanosoma cruzi, the causal agent of Chagas' disease, and other protozoa in terms of both basic and applied science. T. cruzi manifests a great diversity of medical and biological properties which could be the origin of clinical variability in the disease. We propose possible correlations between genetic distances, or phylogenetic divergence, and histopathological data. To ascertain this aspect, 15 cloned stocks pertaining to three major clones or genotypes (19, 20 and 39) were compared. Sets of 24 mice infected with each stock were studied for histopathological lesions. Brain, heart, lung, liver, spleen, urinary bladder, bone marrow, colon, kidney and skeletal muscle were extracted from each mouse. Qualitative and quantitative differences showed at histopathological examination. An important encephalic softening was found in brains of most mice infected by genotype 20, corresponding to areas of inflammation and liquified necrosis. Other inflammatory tissue lesions in the histological sections of the three genotypes were similar. Skeletal muscle tropism was higher than cardiac tropism in all the studied genotypes. All three genotypes shared parasite presence in skeletal muscle. Differences related to cardiac tropism were important: in genotype 19, 50% of studied stocks presented pseudocysts; 20% in genotype 20 and 83% in genotype 39. Parasite presence in other tissues was scanty: in brain only in genotype 20 and in spleen and liver only in genotype 39. We found important histopathogenicity differences among the three studied genotypes, but they do not support the hypothesis of zymodeme pathogenic specificity due to the great diversity among stocks within each genotype.keywords Trypanosoma cruzi, histopathological findings, genotype, genetic divergence correspondence Dr J. A.

Sequence diversity and differential expression of Tc52 immuno-regulatory protein in Trypanosoma cruzi: potential implications in the biological variability of strains

“…The relationship between pathogenicity and T. cruzi genotypes is still debated, with the hypothesis of genotype pathogenic specificity not being supported by the great diversity observed among strains within the same genotype (de Diego et al 1998) and by the differences in infectivity and immunopathology among strains belonging to a same DTU (Garzon et al 2005;Sanchez-Guillen Mdel et al 2006). As the variability of excreted-secreted proteins may be relevant to the biological heterogeneity of T. cruzi, we focused our study on the sequence variability and on the differential expression of Tc52 protein in epidemiologically relevant laboratory clones.…”

“…Studies trying to link the pathogenicity with parasite isolates or laboratory clones of different origins, based on their genetic or evolutionary distances, are controversial. While some studies reported a correlation between the genetic distances and the biological properties of the genotypes (Andrade and Magalhaes 1996;Laurent et al 1997;Revollo et al 1998;Toledo et al 2002), other authors demonstrated significant differences between genetically related T. cruzi clones, well documented in histopathology and other characteristics of murine experimental infections (Carneiro et al 1991;de Diego et al 1998). A few studies focused on the differential gene expression of some T. cruzi factors involved in key events of the parasite life cycle (Ruiz et al 1998;Weston et al 1999;Risso et al 2004).…”

Evaluation of Nifurtimox Treatment of Chronic Chagas Disease by Means of Several Parasitological Methods

“…The clinical manifestations and variations in the immune response observed during chagasic infection are not well understood but are believed to be associated with the host or parasite genetic variability. Several studies involving T. cruzi infection have confirmed that genetic diversity is correlated with intrinsic characteristics of the parasite such as virulence, drug resistance, parasitemia, tissue tropism, pathological alterations, capacity to induce host mortality, and pattern of humoral immune response (26,27,28,29). A further important aspect linked to genetic diversity is the susceptibility of parasites to the two pharmacological therapies that are currently available to treat human Chagas disease, namely, BZ (Roche, São Paulo, Brazil) and NF (Bayer, Leverkusen, Germany).…”

Trypanosoma cruzi: genetic group with peculiar biochemical and biological behavior

“…This clonal model predicts a parallel evolution between biological differences and genetic divergence among T. cruzi natural clones. Some results have shown a strong statistical linkage between genetic and biological differences using T. cruzi cloned stocks representing three or four major clonal geno- types of the parasite (Laurent et al 1997, Revollo et al 1998, Diego et al 1998, Toledo et al 2002, 2003.…”