Abstract
BackgroundThe obligate intracellular parasite Toxoplasma gondii establishes a life-long chronic infection within any warm-blooded host. After ingestion of an encysted parasite, T. gondii disseminates throughout the body as a rapidly replicating form during acute infection. Over time and after stimulation of the host immune response, T. gondii differentiates into a slow growing, cyst form that is the hallmark of chronic infection. Global transcriptome analysis of both host and parasite during the establishment of chronic T. gondii infection has not yet been performed. Here, we conducted a dual RNA-seq analysis of T. gondii and its rodent host to better understand host and parasite responses during acute and chronic infection.ResultsWe obtained nearly one billion paired-end RNA sequences from the forebrains of uninfected, acutely and chronically infected mice, then aligned them to the genomic reference files of both T. gondii and Mus musculus. Gene ontology (GO) analysis of the 100 most highly expressed T. gondii genes showed less than half were shared between acute and chronic infection. The majority of the highly expressed genes common in both acute and chronic infection were involved in transcription and translation, underscoring that parasites in both stages are actively synthesizing proteins. Similarly, most of the T. gondii genes highly expressed during chronic infection were involved in metabolic processes, again highlighting the activity of the cyst stage at 28 days post-infection. Comparative analyses of host genes using uninfected forebrain revealed over twice as many immune regulatory genes were more abundant during chronic infection compared to acute. This demonstrates the influence of parasite development on host gene transcription as well as the influence of the host environment on parasite gene transcription.ConclusionsRNA-seq is a valuable tool to simultaneously analyze host and microbe transcriptomes. Our data shows that T. gondii is metabolically active and synthesizing proteins at 28 days post-infection and that a distinct subset of host genes associated with the immune response are more abundant specifically during chronic infection. These data suggest host and pathogen interplay is still present during chronic infection and provides novel T. gondii targets for future drug and vaccine development.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-806) contains supplementary material, which is available to authorized users.
Highlights
The obligate intracellular parasite Toxoplasma gondii establishes a life-long chronic infection within any warm-blooded host
Type II strains of T. gondii have been detected in the mouse brain as early as 4 days postinfection and numbers continue to increase until 10 days post-infection [23,24], the peak of acute infection [25]
We examined mouse brains at 10 and 28 days postinfection using an In Vivo Imaging System (IVIS), which confirmed that parasites were primarily localized in the forebrains of mice (Figure 1)
Summary
The obligate intracellular parasite Toxoplasma gondii establishes a life-long chronic infection within any warm-blooded host. Toxoplasma gondii is an obligate intracellular parasite that can infect any nucleated cell of warm-blooded animals. T. gondii is one of the most prominent parasites in humans with prevalence rates between 10 and 80 percent worldwide, depending on the country [5] Complications such as hydrocephaly, retinochoroiditis, mental retardation and even death can occur in developing fetuses [6,7]. There are no drugs that can combat the bradyzoite form of the parasite or effective vaccines to protect against infection These issues highlight the critical need to understand the cellular triggers that control development between the tachyzoite and bradyzoite stages
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have