Transcriptome profile of Trypanosoma cruzi-infected cells: simultaneous up- and down-regulation of proliferation inhibitors and promoters.
As Trypanosoma cruzi, the etiological agent of Chagas disease, multiplies in the cytoplasm of nucleated host cells, infection with this parasite is highly likely to affect host cells. We performed an exhaustive transcriptome analysis of T. cruzi-infected HeLa cells using an oligonucleotide microarray containing probes for greater than 47,000 human gene transcripts. In comparison with uninfected cells, those infected with T. cruzi showed greater than threefold up-regulation of 41 genes and greater than threefold down-regulation of 23 genes. Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) of selected, differentially expressed genes confirmed the microarray data. Many of these up- and down-regulated genes were related to cellular proliferation, including seven up-regulated genes encoding proliferation inhibitors and three down-regulated genes encoding proliferation promoters, strongly suggesting that T. cruzi infection inhibits host cell proliferation, which may allow more time for T. cruzi to replicate and produce its intracellular nests. These findings provide new insight into the molecular mechanisms by which intracellular T. cruzi infection influences the host cell, leading to pathogenicity.
Division of Molecular and Biochemical Research, Biomedical Research Center, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
Takako
T
Shigihara
Muneaki
M
Hashimoto
Noriko
N
Shindo
Takashi
T
Aoki
D000818:Animals; D049109:Cell Proliferation; D015536:Down-Regulation; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006367:HeLa Cells / Q000469:parasitology; D006790:Host-Parasite Interactions; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014349:Trypanosoma cruzi / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D015854:Up-Regulation
D011506:Proteins