parasite-induced-genetically-driven-autoimmune-chagas-heart-disease

Parasite Induced Genetically Driven Autoimmune Chagas Heart Disease in the Chicken Model

The Trypanosoma cruzi acute infections acquired in infancy and childhood seem asymptomatic, but approximately one third of the chronically infected cases ...

University of Brasilia

Lack of conservation of the Amazon tropical rainforest has imposed severe threats to its human population living in newly settled villages, resulting in outbreaks of some infectious diseases. We conducted a seroepidemiological survey of 1100 inhabitants of 15 villages of Paço do Lumiar County, Brazil. Thirty-five (3%) individuals had been exposed to Trypanosoma cruzi (Tc), 41 (4%) to Leishmania braziliensis (Lb) and 50 (4.5%) to Leishmania chagasi (Lc) infections. Also, 35 cases had antibodies that were cross-reactive against the heterologous kinetoplastid antigens. Amongst these, the Western blot assays revealed that 11 (1%) had Tc and Lb, that seven (0.6%) had Lc and Tc, and that 17 (1.6%) had Lb and Lc infections. All of these cases of exposures to mixed infections with Leishmania sp, and eight of 11 cases of Tc and Lb were confirmed by specific PCR assays and Southern hybridizations. Two cases had triple infections. We consider these asymptomatic cases showing phenotype and genotype markers consistent with mixed infections by two or more kinetoplastid flagellates a high risk factor for association with Psychodidae and Triatominae vectors blood feeding and transmitting these protozoa infections. This is the first publication showing human exposure to mixed asymptomatic kinetoplastid infections in the Amazon.

Exposure to mixed asymptomatic infections with Trypanosoma cruzi, Leishmania braziliensis and Leishmania chagasi in the human population of the greater Amazon.

Interspecies DNA transfer is a major biological process leading to the accumulation of mutations inherited by sexual reproduction among eukaryotes. Lateral DNA transfer events and their inheritance has been challenging to document. In this study we modified a thermal asymmetric interlaced PCR by using additional targeted primers, along with Southern blots, fluorescence techniques, and bioinformatics, to identify lateral DNA transfer events from parasite to host. Instances of naturally occurring human infections by Trypanosoma cruzi are documented, where mitochondrial minicircles integrated mainly into retrotransposable LINE-1 of various chromosomes. The founders of five families show minicircle integrations that were transferred vertically to their progeny. Microhomology end-joining of 6 to 22 AC-rich nucleotide repeats in the minicircles and host DNA mediates foreign DNA integration. Heterogeneous minicircle sequences were distributed randomly among families, with diversity increasing due to subsequent rearrangement of inserted fragments. Mosaic recombination and hitchhiking on retrotransposition events to different loci were more prevalent in germ line as compared to somatic cells. Potential new genes, pseudogenes, and knockouts were identified. A pathway of minicircle integration and maintenance in the host genome is suggested. Thus, infection by T. cruzi has the unexpected consequence of increasing human genetic diversity, and Chagas disease may be a fortuitous share of negative selection. This demonstration of contemporary transfer of eukaryotic DNA to the human genome and its subsequent inheritance by descendants introduces a significant change in the scientific concept of evolutionary biology and medicine.

Inheritance of DNA transferred from American trypanosomes to human hosts.

The administration of anti-trypanosome nitroderivatives curtails Trypanosoma cruzi infection in Chagas disease patients, but does not prevent destructive lesions in the heart. This observation suggests that an effective treatment for the disease requires understanding its pathogenesis.

Article	Year
The Journal of biological chemistry\| PubMed ID: 14985353	2004
Proteomics\| PubMed ID: 15048986	2004
Journal of proteome research\| PubMed ID: 15253433	2004
Cell\| PubMed ID: 15260988	2004
Insect biochemistry and molecular biology\| PubMed ID: 15475299	2004
MemÃ³rias do Instituto Oswaldo Cruz\| PubMed ID: 15543416	2004
The Biochemical journal\| PubMed ID: 15581422	2005
Microbes and infection / Institut Pasteur\| PubMed ID: 15784182	2005
Infection and immunity\| PubMed ID: 15784569	2005
The Biochemical journal\| PubMed ID: 16542158	2006
Microbes and infection / Institut Pasteur\| PubMed ID: 16979366	2006
MemÃ³rias do Instituto Oswaldo Cruz\| PubMed ID: 17072450	2006
The American journal of tropical medicine and hygiene\| PubMed ID: 17123983	2006
MemÃ³rias do Instituto Oswaldo Cruz\| PubMed ID: 17293976	2006
Exposure to mixed asymptomatic infections with Trypanosoma cruzi, Leishmania braziliensis and Leishmania chagasi in the human population of the greater Amazon. Tropical medicine & international health : TM & IH\| PubMed ID: 17445130	2007
Proteome science\| PubMed ID: 18778485	2008
Cadernos de saÃºde pÃºblica / MinistÃ©rio da SaÃºde, FundaÃ§Ã£o Oswaldo Cruz, Escola Nacional de SaÃºde PÃºblica\| PubMed ID: 19287864	2009
Inheritance of DNA transferred from American trypanosomes to human hosts. PloS one\| PubMed ID: 20169193	2010
Journal of proteomics\| PubMed ID: 21362504	2011
Trypanosoma cruzi in the chicken model: Chagas-like heart disease in the absence of parasitism. PLoS neglected tropical diseases\| PubMed ID: 21468314	2011
Journal of proteomics\| PubMed ID: 21601023	2011
Clinical microbiology reviews\| PubMed ID: 21734249	2011
Journal of proteomics\| PubMed ID: 21742069	2011
PLoS neglected tropical diseases\| PubMed ID: 21912712	2011
Journal of proteomics\| PubMed ID: 22579750	2012

Antonio R. L. Teixeira

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