Titre:	Lesões típicas da Doença de Chagas em aves com genoma alterado por integração de seqüências de minicírculos de kDNA de Trypanosoma cruzi
Auteur(s):	Cardoso, Clever Gomes
Orientador(es)::	Teixeira, Antônio Raimundo Lima Cruz
Assunto::	Tripanossoma cruzi Genomas Genética Chagas, Doença de Aves
Date de publication:	3-déc-2009
Data de defesa::	2006
Référence bibliographique:	CARDOSO, Clever Gomes. Lesões típicas da Doença de Chagas em aves com genoma alterado por integração de seqüências de minicírculos de kDNA de Trypanosoma cruzi. 2006. 131 f. Tese (Doutorado em Patologia Molecular)-Universidade de Brasília, Brasília, 2006.
Abstract:	It has been said that origin and evolution of live organisms were anticipated by network interactions among molecules, microorganisms and cells into complex metazoa. It appears, in this process took place countless events of horizontal transfer of DNA (HGT) amongst species far distant in the phylogenetic tree, thus promoting increasing complexity of the existing organism genomes. The accumulation of DNA molecules in the eukaryote cell nucleus led to sustainable genetic inheritance, thus portraying a main pathway for the evolution of species. Within this framework, the research reported herein is consistent with the idea that genomes from eukaryotes can receive continuous flow of DNA by HGT. Furthermore, it has also been shown that HGT molecules can be inherited vertically (VGT) by the progeny. These observations are in keeping with previous evidence showing prokaryote orthologues that would have been inherited by eukaryotes. Although until recently HGT had been considered a rare event that took place in early epochs, as suggested by the evidence recently found in the vertebrate’s genome sequencing databank, the research carried out in our Laboratory shows that HGT is indeed a mostly expected event, which could be consistently demonstrated in vitro and in vivo. This demonstration does not confirm a previous concept describing HGT as a rare event, which would occur at a rather low frequency. The data reported here shows that HGT can be detected in each host cell undergoing T. cruzi infections and, therefore HGT was shown in a high ratio of chicks born from T. cruzi–infected eggs. In conjunction, our previous studies have shown a gamut of HGT in different in vitro and in vivo models depicting DNA transfer from eukaryote to eukaryote. The work presented here shows sequences of kDNA minicircles from T. cruzi integrated (HGT) within the chicken genome. Furthermore, crossings of kDNA-positive birds resulted in the transfer of the kDNA integrations (VGT) to progeny. The chickens are refractory to the T. cruzi infections, although the infections could get established in early stages of the embryos; after ten days of incubation the T. cruzi infection could be eliminated by the embryo innate immune response. We verified that in the crucial early period of the infection and embryo development the chick stem cells can be T. cruzi-infected. Thereafter host cell and parasite undergoing accelerated multiplication created the grounds for HGT. The demonstration of HGT of sequences of minicircles of kDNA to the chicken genome represents a clean biological system, since birds are refractory to T. cruzi. Accordingly, the chicken model allowed the study of the kDNA-integration that generate genotype alterations and pathology similar to those described in human Chagas disease. Besides, we have demonstrated VGT by the crossings of kDNA-positive birds, which yielded kDNA-integrated progeny. The kDNA-positive F1, F2 e F3 birds were obtained and proved to carry VGT through the kDNA integrations in male and female gametes. The kDNA-integrated birds (F0, F1, F2 e F3) developed clinical signals typical of Chagas disease: destructive lesions were documented in the striated skeletal and heart muscles, in the smooth muscles and in the parasympathetic ganglia. In the kDNA-integrated but parasite-free birds there were minimal rejection units characterized by the immune system mononuclear cell infiltrates and lyses of the host’s self target cells. The confluence of a gamut of minimal rejection units did reproduce a typical diffuse myocarditis hallmark of Chagas disease affecting mammal hosts. These results show that genomic alterations stemming form kDNA insertion-mutation can provoke auto-immune rejection of host tissues. In fact, the documentation of severe Chagas lesions in kDNA-integrated birds is consistent with our hypothesis that the T. cruzi is vector of a genetic disease. Further studies are required to unravel the practical consequences resulting from the T. cruzi kDNA integration in the parasite-free host organism. Such demonstrate could ultimately show much such kDNA integrations contribute to the development of pathological lesions typical of Chagas disease. Moreover, these studies could elucidate the molecular mechanisms of pathogenesis calling forth auto-immunity in Chagas disease.
metadata.dc.description.unidade:	Faculdade de Medicina (FM)
Description:	Tese (doutorado)—Universidade de Brasília, Faculdade de Medicina, 2006.
metadata.dc.description.ppg:	Programa de Pós-Graduação em Patologia Molecular
Collection(s) :	Teses, dissertações e produtos pós-doutorado

Tous les documents dans DSpace sont protégés par copyright, avec tous droits réservés.