Evolution and pathology in Chagas disease - A Review

Trypansoma cruzi acute infections often go unperceived, but one third of chronically infected individuals die of Chagas disease, showing diverse manifestations affecting the heart, intestines, and nervous systems. A common denominator of pathology in Chagas disease is the minimal rejection unit, whe...

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Bibliographic Details
Published in:Memórias do Instituto Oswaldo Cruz 2006-08, Vol.101 (5), p.463-491
Main Authors: Teixeira, Antonio R L, Nascimento, Rubens J, Sturm, Nancy R
Format: Article
Language:English
Subjects:
Acute Disease
Animals
Biological Evolution
Birds
Chagas Disease - genetics
Chagas Disease - immunology
Chagas Disease - pathology
Chronic Disease
DNA, Kinetoplast - genetics
genome growth
horizontal transfer
Humans
kDNA-mutation
kinetoplast DNA
Mammals
Mutation
PARASITOLOGY
pathology
Phenotype
TROPICAL MEDICINE
Trypanosoma cruzi
Trypanosoma cruzi - genetics
Trypanosoma cruzi - immunology
Trypanosoma cruzi - kinetoplast DNA - horizontal transfer - genome growth - kDNA-mutation - pathology
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Summary:Trypansoma cruzi acute infections often go unperceived, but one third of chronically infected individuals die of Chagas disease, showing diverse manifestations affecting the heart, intestines, and nervous systems. A common denominator of pathology in Chagas disease is the minimal rejection unit, whereby parasite-free target host cells are destroyed by immune system mononuclear effectors cells infiltrates. Another key feature stemming from T. cruzi infection is the integration of kDNA minicircles into the vertebrate host genome; horizontal transfer of the parasite DNA can undergo vertical transmission to the progeny of mammals and birds. kDNA integration-induced mutations can enter multiple loci in diverse chromosomes, generating new genes, pseudo genes and knock-outs, and resulting in genomic shuffling and remodeling over time. As a result of the juxtaposition of kDNA insertions with host open reading frames, novel chimeric products may be generated. Germ line transmission of kDNA-mutations determined the appearance of lesions in birds that are indistinguishable from those seen in Chagas disease patients. The production of tissue lesions showing typical minimal rejection units in birds' refractory to T. cruzi infection is consistent with the hypothesis that autoimmunity, likely triggered by integration-induced phenotypic alterations, plays a major role in the pathogenesis of Chagas disease.
ISSN:1678-8060
0074-0276
0074-0276
1678-8060
DOI:10.1590/s0074-02762006000500001