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      Advances towards the complete in vitro life cycle of Toxoplasma gondii


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          The full life cycle of Toxoplasma gondii cannot be recapitulated in vitro, and access to certain stages, such as mature tissue cysts (bradyzoites) and oocysts (sporozoites), traditionally requires animal experiments. This has greatly hindered the study of the biology of these morphologically and metabolically distinct stages, which are essential for the infection of humans and animals. However, several breakthrough advances have been made in recent years towards obtaining these life stages in vitro, such as the discovery of several molecular factors that induce differentiation and commitment to the sexual cycle, and different culture methods that use, for example, myotubes and intestinal organoids to obtain mature bradyzoites and different sexual stages of the parasite. We review these novel tools and approaches, highlight their limitations and challenges, and discuss what research questions can already be answered with these models. We finally identify future routes for recapitulating the entire sexual cycle in vitro.

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          Modeling Development and Disease with Organoids.

          Recent advances in 3D culture technology allow embryonic and adult mammalian stem cells to exhibit their remarkable self-organizing properties, and the resulting organoids reflect key structural and functional properties of organs such as kidney, lung, gut, brain and retina. Organoid technology can therefore be used to model human organ development and various human pathologies 'in a dish." Additionally, patient-derived organoids hold promise to predict drug response in a personalized fashion. Organoids open up new avenues for regenerative medicine and, in combination with editing technology, for gene therapy. The many potential applications of this technology are only beginning to be explored.
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            Structures of Toxoplasma gondii tachyzoites, bradyzoites, and sporozoites and biology and development of tissue cysts.

            Infections by the protozoan parasite Toxoplasma gondii are widely prevalent world-wide in animals and humans. This paper reviews the life cycle; the structure of tachyzoites, bradyzoites, oocysts, sporocysts, sporozoites and enteroepithelial stages of T. gondii; and the mode of penetration of T. gondii. The review provides a detailed account of the biology of tissue cysts and bradyzoites including in vivo and in vitro development, methods of separation from host tissue, tissue cyst rupture, and relapse. The mechanism of in vivo and in vitro stage conversion from sporozoites to tachyzoites to bradyzoites and from bradyzoites to tachyzoites to bradyzoites is also discussed.
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              Epidemiology of and diagnostic strategies for toxoplasmosis.

              The apicomplexan parasite Toxoplasma gondii was discovered a little over 100 years ago, but knowledge of its biological life cycle and its medical importance has grown in the last 40 years. This obligate intracellular parasite was identified early as a pathogen responsible for congenital infection, but its clinical expression and the importance of reactivations of infections in immunocompromised patients were recognized later, in the era of organ transplantation and HIV infection. Recent knowledge of host cell-parasite interactions and of parasite virulence has brought new insights into the comprehension of the pathophysiology of infection. In this review, we focus on epidemiological and diagnostic aspects, putting them in perspective with current knowledge of parasite genotypes. In particular, we provide critical information on diagnostic methods according to the patient's background and discuss the implementation of screening tools for congenital toxoplasmosis according to health policies.

                Author and article information

                Fac Rev
                Fac Rev
                Faculty Reviews
                Faculty Opinions Ltd (London, UK )
                13 February 2023
                : 12
                : 1
                [1 ]FG16: Mycotic and Parasitic Agents and Mycobacteria, Robert Koch-Institut, Berlin, Germany
                Author notes

                The authors have no personal or financial competing interests to declare.

                Copyright: © 2023 Seeber F et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Funded by: Deutsche Forschungsgemeinschaft (DFG)
                Award ID: 251133687/GRK 2046
                Funded by: European Union’s Horizon 2020 Research and Innovation program
                Award ID: 773830
                Funded by: Robert Koch-Institut
                DW is a member of the Research Training Group 2046 “Parasite Infections: From Experimental Models to Natural Systems” funded by the Deutsche Forschungsgemeinschaft (DFG), project number 251133687/GRK 2046. FS is a member of TOXOSOURCES (supported by funding from the European Union’s Horizon 2020 Research and Innovation program under grant agreement no. 773830: One Health European Joint Program). Work of FS is also supported by the Robert Koch-Institut.
                Review Article

                toxoplasma gondii,toxoplasmosis,life cycle,in vitro model,organoids,bradyzoites,oocysts


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