Evolution and pathology in chagas disease--a review.
Trypanosoma 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.
Teixeira
Antonio R L
AR
Laboratório de Pesquisa Multidisciplinar em Doença de Chagas, Faculdade de Medicina, Universidade de Brasilia, Caixa Postal 04536, 70919-970 Brasilia,-DF, Brasil. ateixeir@unb.br
Nascimento
Rubens J
RJ
Sturm
Nancy R
NR
D000208:Acute Disease; D000818:Animals; D005075:Biological Evolution; D001717:Birds; D014355:Chagas Disease / Q000235:genetics* / Q000276:immunology / Q000473:pathology*; D002908:Chronic Disease; D018105:DNA, Kinetoplast / Q000235:genetics*; D006801:Humans; D008322:Mammals; D009154:Mutation; D010641:Phenotype; D014349:Trypanosoma cruzi / Q000235:genetics* / Q000276:immunology
D018105:DNA, Kinetoplast