Abstract
Trypanosoma cruzi, the causative agent of Chagas Disease, is phylogeneticaly distributed into nearly identical genetic strains which show divergent clinical presentations including differences in rates of cardiomyopathy in humans, different vector species and transmission cycles, differential congenital transmission in a mouse model, and differing immune and heart inflammation response in dogs. The population structure of these strains divides into two groups, which are geographically and clinically distinct. The aim of this study was to compare the transcriptome of two strains of T. cruzi, Sylvio vs. Y, to identify differences in expression that could account for clinical and biochemical differences. We collected and sequenced RNA from T. cruzi-infected and control Human Foreskin Fibroblasts at three timepoints. Differential expression analysis identified gene expression different timepoints in Sylvio infections, and between Sylvio and Y infections in both parasite and host. The Sylvio strain parasite and the host response to Sylvio infection largely mirrored the host-pathogen interaction seen in our previous Y strain work. IL-8 was more highly expressed in Sylvio-infected HFFs than in Y-infected HFFs.
Highlights
Trypanosoma cruzi, a protozoan parasite, is the causative agent of Chagas Disease, a disease which affects 6–7 million people primarily in Latin America. [1] The parasite is transmitted by a triatomine insect vector, where it is introduced into the host by the feces of the insect as it takes a blood meal
We investigated whether we could detect differences in the global transcriptomes of two T. cruzi strains: Sylvio (DTU I) and Y (DTU II), as well as host cells given the distinct clinical and biochemical profiles suggested by previous reports
Two independent Sylvio infections were carried out in human foreskin fibroblasts (HFF) cells and RNA was harvested from pre-infection tissue culture trypomastigotes (TCT) as well as infected cells; these were matched with uninfected control cells at 4, 24 and 72 hpi
Summary
Trypanosoma cruzi, a protozoan parasite, is the causative agent of Chagas Disease, a disease which affects 6–7 million people primarily in Latin America. [1] The parasite is transmitted by a triatomine insect vector, where it is introduced into the host by the feces of the insect as it takes a blood meal. Trypanosoma cruzi, a protozoan parasite, is the causative agent of Chagas Disease, a disease which affects 6–7 million people primarily in Latin America. The drugs are fairly effective if taken during the early (acute) stage of the disease, with limited utility in the chronic stages of the disease. 30% of infected individuals will develop chronic Chagas Disease, which can manifest as inflammatory heart disease, and/or gastrointestinal disease leading to megacolon or megaesophagus. Comparative Transcriptome Profiling of Two Strains of Trypanosoma cruzi Infecting Human Host Cells. T. cruzi reproduces clonally, but there appears to be at least one historical hybridization event leading to strains with different haplotypes. [3] While there is some debate as to the number of hybridization events that have occurred to produce the heterozygous strains in DTUs V and VI, there is broad agreement that DTUs I and II are pure ancient lineages. The population structure is described by assigning the various strains of T. cruzi into six discrete typing units (DTUs) based on molecular markers. [3] While there is some debate as to the number of hybridization events that have occurred to produce the heterozygous strains in DTUs V and VI, there is broad agreement that DTUs I and II are pure ancient lineages. [4]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call