Uncovering biomarkers for chronic toxoplasmosis detection highlights alternative pathways shaping parasite dormancy
Abstract Toxoplasma gondii, a neurotropic protozoan, causes toxoplasmosis, a prevalent zoonotic and food-borne infection, posing significant risks to immunocompromised individuals and congenital cases. The chronic phase, characterized by dormant, cyst-forming bradyzoites, is central to disease progr...
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Springer Nature
2025-05-01
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| Series: | EMBO Molecular Medicine |
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| Online Access: | https://doi.org/10.1038/s44321-025-00252-0 |
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| author | Marie G Robert Christopher Swale Belen Pachano Léa Dépéry Valeria Bellini Céline Dard Dominique Cannella Charlotte Corrao Lucid Belmudes Yohann Couté Alexandre Bougdour Hervé Pelloux Emmanuelle Chapey Martine Wallon Marie-Pierre Brenier-Pinchart Mohamed-Ali Hakimi |
| author_facet | Marie G Robert Christopher Swale Belen Pachano Léa Dépéry Valeria Bellini Céline Dard Dominique Cannella Charlotte Corrao Lucid Belmudes Yohann Couté Alexandre Bougdour Hervé Pelloux Emmanuelle Chapey Martine Wallon Marie-Pierre Brenier-Pinchart Mohamed-Ali Hakimi |
| author_sort | Marie G Robert |
| collection | DOAJ |
| description | Abstract Toxoplasma gondii, a neurotropic protozoan, causes toxoplasmosis, a prevalent zoonotic and food-borne infection, posing significant risks to immunocompromised individuals and congenital cases. The chronic phase, characterized by dormant, cyst-forming bradyzoites, is central to disease progression but is poorly understood due to the lack of serological tests to detect bradyzoite-specific antigens. This study identifies the bradyzoite serological marker (BSM) and cyst-associated BCLA as effective biomarkers for chronic toxoplasmosis. These markers showed high sensitivity and specificity in detecting cyst-bearing mice and had a positivity rate of 30% in humans with prior immunity. Bradyzoite serology helps to discriminate between recent and past infections, with BCLA improving the accuracy of the diagnosis of congenital infections. Mechanistic analyses show that the chromatin modifiers MORC and HDAC3 epistatically regulate BFD1, a key bradyzoite regulator. While BFD1 controls the expression of bradyzoite genes such as BCLA, a specific subset, including BSM, is regulated independently of BFD1. This multilayered regulation complicates the understanding of parasite persistence in humans, but offers promise for improved serologic diagnosis during pregnancy, but also in individuals with mental illness. |
| format | Article |
| id | doaj-art-ad44646c80f74d4ea51a7a11ed51a3fb |
| institution | Kabale University |
| issn | 1757-4684 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj-art-ad44646c80f74d4ea51a7a11ed51a3fb2025-08-20T03:42:52ZengSpringer NatureEMBO Molecular Medicine1757-46842025-05-011771686171510.1038/s44321-025-00252-0Uncovering biomarkers for chronic toxoplasmosis detection highlights alternative pathways shaping parasite dormancyMarie G Robert0Christopher Swale1Belen Pachano2Léa Dépéry3Valeria Bellini4Céline Dard5Dominique Cannella6Charlotte Corrao7Lucid Belmudes8Yohann Couté9Alexandre Bougdour10Hervé Pelloux11Emmanuelle Chapey12Martine Wallon13Marie-Pierre Brenier-Pinchart14Mohamed-Ali Hakimi15Team Host-Pathogen Interactions and Immunity to Infection, Institute for Advanced Biosciences, INSERM U1209, CNRS UMR5309, Grenoble Alpes UniversityTeam Host-Pathogen Interactions and Immunity to Infection, Institute for Advanced Biosciences, INSERM U1209, CNRS UMR5309, Grenoble Alpes UniversityTeam Host-Pathogen Interactions and Immunity to Infection, Institute for Advanced Biosciences, INSERM U1209, CNRS UMR5309, Grenoble Alpes UniversityTeam Host-Pathogen Interactions and Immunity to Infection, Institute for Advanced Biosciences, INSERM U1209, CNRS UMR5309, Grenoble Alpes UniversityTeam Host-Pathogen Interactions and Immunity to Infection, Institute for Advanced Biosciences, INSERM U1209, CNRS UMR5309, Grenoble Alpes UniversityTeam Host-Pathogen Interactions and Immunity to Infection, Institute for Advanced Biosciences, INSERM U1209, CNRS UMR5309, Grenoble Alpes UniversityTeam Host-Pathogen Interactions and Immunity to Infection, Institute for Advanced Biosciences, INSERM U1209, CNRS UMR5309, Grenoble Alpes UniversityTeam Host-Pathogen Interactions and Immunity to Infection, Institute for Advanced Biosciences, INSERM U1209, CNRS UMR5309, Grenoble Alpes UniversityGrenoble Alpes University, INSERM, CEA, UA13 BGE, CNRS, CEA, FR2048Grenoble Alpes University, INSERM, CEA, UA13 BGE, CNRS, CEA, FR2048Team Host-Pathogen Interactions and Immunity to Infection, Institute for Advanced Biosciences, INSERM U1209, CNRS UMR5309, Grenoble Alpes UniversityTeam Host-Pathogen Interactions and Immunity to Infection, Institute for Advanced Biosciences, INSERM U1209, CNRS UMR5309, Grenoble Alpes UniversityHospices Civils de Lyon, Institut des Agents InfectieuxHospices Civils de Lyon, Institut des Agents InfectieuxTeam Host-Pathogen Interactions and Immunity to Infection, Institute for Advanced Biosciences, INSERM U1209, CNRS UMR5309, Grenoble Alpes UniversityTeam Host-Pathogen Interactions and Immunity to Infection, Institute for Advanced Biosciences, INSERM U1209, CNRS UMR5309, Grenoble Alpes UniversityAbstract Toxoplasma gondii, a neurotropic protozoan, causes toxoplasmosis, a prevalent zoonotic and food-borne infection, posing significant risks to immunocompromised individuals and congenital cases. The chronic phase, characterized by dormant, cyst-forming bradyzoites, is central to disease progression but is poorly understood due to the lack of serological tests to detect bradyzoite-specific antigens. This study identifies the bradyzoite serological marker (BSM) and cyst-associated BCLA as effective biomarkers for chronic toxoplasmosis. These markers showed high sensitivity and specificity in detecting cyst-bearing mice and had a positivity rate of 30% in humans with prior immunity. Bradyzoite serology helps to discriminate between recent and past infections, with BCLA improving the accuracy of the diagnosis of congenital infections. Mechanistic analyses show that the chromatin modifiers MORC and HDAC3 epistatically regulate BFD1, a key bradyzoite regulator. While BFD1 controls the expression of bradyzoite genes such as BCLA, a specific subset, including BSM, is regulated independently of BFD1. This multilayered regulation complicates the understanding of parasite persistence in humans, but offers promise for improved serologic diagnosis during pregnancy, but also in individuals with mental illness.https://doi.org/10.1038/s44321-025-00252-0BradyzoiteEpigeneticsSerologyToxoplasma gondiiTranscription |
| spellingShingle | Marie G Robert Christopher Swale Belen Pachano Léa Dépéry Valeria Bellini Céline Dard Dominique Cannella Charlotte Corrao Lucid Belmudes Yohann Couté Alexandre Bougdour Hervé Pelloux Emmanuelle Chapey Martine Wallon Marie-Pierre Brenier-Pinchart Mohamed-Ali Hakimi Uncovering biomarkers for chronic toxoplasmosis detection highlights alternative pathways shaping parasite dormancy EMBO Molecular Medicine Bradyzoite Epigenetics Serology Toxoplasma gondii Transcription |
| title | Uncovering biomarkers for chronic toxoplasmosis detection highlights alternative pathways shaping parasite dormancy |
| title_full | Uncovering biomarkers for chronic toxoplasmosis detection highlights alternative pathways shaping parasite dormancy |
| title_fullStr | Uncovering biomarkers for chronic toxoplasmosis detection highlights alternative pathways shaping parasite dormancy |
| title_full_unstemmed | Uncovering biomarkers for chronic toxoplasmosis detection highlights alternative pathways shaping parasite dormancy |
| title_short | Uncovering biomarkers for chronic toxoplasmosis detection highlights alternative pathways shaping parasite dormancy |
| title_sort | uncovering biomarkers for chronic toxoplasmosis detection highlights alternative pathways shaping parasite dormancy |
| topic | Bradyzoite Epigenetics Serology Toxoplasma gondii Transcription |
| url | https://doi.org/10.1038/s44321-025-00252-0 |
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