Determination of a Key Antigen for Immunological Intervention To Target the Latent Stage of Toxoplasma gondii
| Autor: | Corinne Mercier, Ashish Tiwari, Marie-France Cesbron-Delauw, Jeremi Mullins, Eri Ochiai, Nilabh Shastri, Yasuhiro Suzuki, Qila Sa |
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| Přispěvatelé: | Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky, Division of Immunology and Pathogenesis (Department of Molecular and Cell Biology), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Barrière Naturelle et Infectiosité (TIMC-IMAG-BNI), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Bisanz, Cordelia |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
030106 microbiology Immunology Population Protozoan Proteins Antigens Protozoan CD8-Positive T-Lymphocytes Article Mice 03 medical and health sciences Immune system Antigen parasitic diseases Animals Immunology and Allergy education [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology education.field_of_study biology T-cell receptor Brain Toxoplasma gondii biology.organism_classification Virology 3. Good health Chronic infection Toxoplasmosis Animal 030104 developmental biology [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology Immunization Toxoplasmosis Cerebral Toxoplasma CD8 |
| Zdroj: | Journal of Immunology Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2017, 198 (11), pp.4425-4434 |
| ISSN: | 0022-1767 1550-6606 |
| Popis: | Toxoplasma gondii, an obligate intracellular protozoan parasite, establishes a chronic infection by forming cysts preferentially in the brain. Up to one third of the human population worldwide is estimated to be chronically infected with this parasite. However, there is currently no drug effective against the cyst form of the parasite. In addition, the protective immunity against the cysts remains largely unknown. We analyzed the molecular mechanisms by which the immune system detects host cells harboring the cysts to eliminate the latent stage of the parasite using mice with the H-2d haplotype, which are genetically resistant to the infection. Our study revealed that CD8+ immune T cells bearing TCR Vβ8.1, 8.2 chain have a potent activity to remove T. gondii cysts from the brain. Our studies also uncovered that H-2Ld is the major Ag-presenting molecule to CD8+ T cells for initiating cyst elimination, and that CD8+Vβ8.1, 8.2+ immune T cells recognize the N-terminal region (aa 41–152) of dense granule protein 6 (GRA6Nt) of the parasite presented by the H-2Ld molecule. Furthermore, CD8+ immune T cells induced by immunization with recombinant GRA6Nt were eventually capable of removing the cysts from the brain when transferred to infected immunodeficient mice lacking T cells. Thus, GRA6Nt is a novel and potent Ag to activate CD8+ T cells capable of removing T. gondii cysts. These observations offer a basis for immunological intervention to combat chronic infection with T. gondii by targeting the persistent cysts of the parasite. |
| Databáze: | OpenAIRE |
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