Transcriptome analysis of alternative splicing in the pathogen life cycle in human foreskin fibroblasts infected with Trypanosoma cruzi

Hyeim Jung,Seonggyun Han,Younghee Lee

doi:10.1038/s41598-020-74540-9

Hyeim Jung, Seonggyun Han + Show 1 more

Open Access

https://doi.org/10.1038/s41598-020-74540-9

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Abstract

Trypanosoma cruzi is an intracellular protozoan parasite that causes Chagas disease as a zoonotic pathogen. The parasite has been shown to remodel expression in the host transcriptome under different conditions. Although alternative splicing (AS) is involved in virtually every biological function in eukaryotes, including cellular differentiation and responses to immune reactions, host AS events that occur as a result of T. cruzi infection have yet to be explored. In this study, we bioinformatically investigated the transcriptome AS dynamics of T. cruzi (Y strain) infected human foreskin fibroblasts using RNA-Seq data captured over four timepoints (4, 24, 48, and 72 h post infection (hpi)). We identified 1768, 399, 250, and 299 differentially expressed exons (AS exons) at 4, 24, 48, and 72 hpi, respectively, showing that host AS mechanism may have a significant role in the intracellular life cycle of the parasite. We present an exon skipping event in HDAC7, which is a candidate gene that is important in the parasite’s cell cycle. To sum up, this bioinformatics analysis of transcriptome may provide new potential insight into AS regulation in human foreskin fibroblast (HFF) cells infected by T. cruzi and into its implication to the parasite life cycle. Moreover, identified AS genes may provide new potential molecular candidates for improving treatment.

Highlights

Trypanosoma cruzi is an intracellular protozoan parasite that causes Chagas disease as a zoonotic pathogen
Genes related to energy metabolism, immune response, and cell cycle were significantly remodeled at the transcript level in infected human foreskin fibroblasts (HFFs), and the
Dynamic changes of alternative splicing occur in human foreskin fibroblasts infected with T. cruzi

Summary

Introduction

Trypanosoma cruzi is an intracellular protozoan parasite that causes Chagas disease as a zoonotic pathogen. Alternative splicing (AS) is involved in virtually every biological function in eukaryotes, including cellular differentiation and responses to immune reactions, host AS events that occur as a result of T. cruzi infection have yet to be explored. We present an exon skipping event in HDAC7, which is a candidate gene that is important in the parasite’s cell cycle To sum up, this bioinformatics analysis of transcriptome may provide new potential insight into AS regulation in human foreskin fibroblast (HFF) cells infected by T. cruzi and into its implication to the parasite life cycle. Trypanosoma cruzi is an intracellular parasite with a complex life cycle that replicates and survives in diverse nucleated host cells including those of the heart and intestinal tract. Investigating dynamic transcriptomic profiles of infected host cells can confer new insights into molecular mechanisms underlying the parasite’s life cycle and potentially identify new molecular targets for improved treatments. Genome-wide analysis of AS in host cells infected with T. cruzi has not yet to be performed

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