Identification of Oocyst-Driven Toxoplasma gondii Infections in Humans and Animals through Stage-Specific Serology—Current Status and Future Perspectives

Abstract

The apicomplexan zoonotic parasite Toxoplasma gondii has three infective stages: sporozoites in sporulated oocysts, which are shed in unsporulated form into the environment by infected felids; tissue cysts containing bradyzoites, and fast replicating tachyzoites that are responsible for acute toxoplasmosis. The contribution of oocysts to infections in both humans and animals is understudied despite being highly relevant. Only a few diagnostic antigens have been described to be capable of discriminating which parasite stage has caused an infection. Here we provide an extensive overview of the antigens and serological assays used to detect oocyst-driven infections in humans and animals according to the literature. In addition, we critically discuss the possibility to exploit the increasing knowledge of the T. gondii genome and the various ‘omics datasets available, by applying predictive algorithms, for the identification of new oocyst-specific proteins for diagnostic purposes. Finally, we propose a workflow for how such antigens and assays based on them should be evaluated to ensure reproducible and robust results.

Factors influencing tissue cyst yield in a murine model of chronic toxoplasmosis

“…Toxoplasma gondii is an important opportunistic infection in the context of HIV-AIDS and other immunosuppressive conditions (1, 2). Transmission of the parasite is mediated by two distinct encysted forms, the oocysts, shed at the end of the sexual cycle in the feces of the definitive feline host (3, 4) and the tissue cysts formed with the establishment of the chronic infection in all vertebrate hosts (5). The tropism of tissue cysts to the central nervous system and muscle provides a mechanism of transmission in the act of carnivory (6, 7).…”

Advances towards the complete in vitro life cycle of Toxoplasma gondii

“…For instance, a sexual stage-specific mRNA expressed upon inhibitor treatment could be useful for convenient development and validation of primers used for reverse transcription quantitative PCR, without a need to obtain or isolate the respective parasite stage. As a surrogate for oocyst/sporozoite proteins, HDAC3-inhibited tachyzoites might be explored to identify appropriate proteins for vaccination 87 or as a source for oocyst-specific diagnostic antigens 88 . The inhibitors could conceivably also be of use for studying protein-protein interactions specific to sexual stages and oocysts, provided that proper controls are implemented.…”

AP2XII-2 coordinates transcriptional repression forToxoplasma gondiisexual commitment

“…In contrast, our understanding of the molecular mechanisms governing the rewiring of gene expression during Toxoplasma sexual development is far less developed, largely due to a lack of model systems. This is despite evidence showing that ingestion of the ultimate product of Toxoplasma sexual reproduction, sporulated oocysts, accounts for a substantial portion of worldwide human infections and mass outbreaks of acute toxoplasmosis (8, 9).…”