Genomic insights into host and parasite interactions during intracellular infection by Toxoplasma gondii

Abstract

To gain insights into the molecular interactions of an intracellular pathogen and its host cell, we studied the gene expression and chromatin states of human fibroblasts infected with the Apicomplexan parasiteToxoplasma gondii. We show a striking activation of host cell genes that regulate a number of cellular processes, some of which are protective of the host cell, others likely to be advantageous to the pathogen. The simultaneous capture of host and parasite genomic information allowed us to gain insights into the regulation of theT.gondiigenome. We show how chromatin accessibility and transcriptional profiling together permit novel annotation of the parasite’s genome, including more accurate mapping of known genes and the identification of new genes andcis-regulatory elements. Motif analysis reveals not only the knownT.gondiiAP2 transcription factor-binding site but also a previously-undiscovered candidate TATA box-containing motif at one-quarter of promoters. By inferring the transcription factor and upstream cell signaling responses involved in the host cell, we can use genomic information to gain insights intoT.gondii’sperturbation of host cell physiology. Our resulting model builds on previously-described human host cell signalling responses toT.gondiiinfection, linked to induction of specific transcription factors, some of which appear to be solely protective of the host cell, others of which appear to be co-opted by the pathogen to enhance its own survival.