Immunological Molecular Responses of Human Retinal Pigment Epithelial Cells to Infection With Toxoplasma gondii

We present a transcriptomic view of the epithelial cell response to infection with T. gondii. RNA-Sequencing of total and small RNA extracted from three human primary retinal pigment epithelial isolates infected with virulent, natural GT-1 strain tachyzoites enabled in silico differential expression, and gene ontology, pathway and network enrichment analyses. Our work revealed a sizeable molecular response in the total RNA transcriptome—with significantly differentially expressed genes totaling 28.9% of total assigned transcripts—but very limited consistent changes in the small RNA transcriptome—totaling 0.35% of assigned transcripts. Gene ontology and pathway studies of differentially expressed total RNA identified a strong immune response signature, which we validated by RT-qPCR for multiple immune response-related protein-coding and long non-coding transcripts in human retinal pigment epithelial cells isolated from three independent donors. By performing biological network analyses within the InnateDB systems immunology platform we identified contextural hubs and subnetworks that illuminated the global immune response to the parasite. The human retinal pigment epithelial cell total RNA transcriptome was substantially impacted by infection with T. gondii: approximately one-third of transcripts were significantly up- or down-regulated, with over 10% of transcripts having greater than two-fold change. T. gondii may infect any nucleated cells, but in v...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research