Robust Control of a Brain-Persisting Parasite through MHC I Presentation by Infected Neurons
Summary: Control of CNS pathogens by CD8 T cells is key to avoid fatal neuroinflammation. Yet, the modalities of MHC I presentation in the brain are poorly understood. Here, we analyze the antigen presentation mechanisms underlying CD8 T cell-mediated control of the Toxoplasma gondii parasite in the...
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doaj-2373147ad458415abbbf727de4dc16e12020-11-24T22:15:13ZengElsevierCell Reports2211-12472019-06-01271132543268.e8Robust Control of a Brain-Persisting Parasite through MHC I Presentation by Infected NeuronsAnna Salvioni0Marcy Belloy1Aurore Lebourg2Emilie Bassot3Vincent Cantaloube-Ferrieu4Virginie Vasseur5Sophie Blanié6Roland S. Liblau7Elsa Suberbielle8Ellen A. Robey9Nicolas Blanchard10Center for Pathophysiology Toulouse-Purpan (CPTP), INSERM, CNRS, University of Toulouse, 31024 Toulouse, FranceCenter for Pathophysiology Toulouse-Purpan (CPTP), INSERM, CNRS, University of Toulouse, 31024 Toulouse, FranceCenter for Pathophysiology Toulouse-Purpan (CPTP), INSERM, CNRS, University of Toulouse, 31024 Toulouse, FranceCenter for Pathophysiology Toulouse-Purpan (CPTP), INSERM, CNRS, University of Toulouse, 31024 Toulouse, FranceCenter for Pathophysiology Toulouse-Purpan (CPTP), INSERM, CNRS, University of Toulouse, 31024 Toulouse, FranceCenter for Pathophysiology Toulouse-Purpan (CPTP), INSERM, CNRS, University of Toulouse, 31024 Toulouse, FranceCenter for Pathophysiology Toulouse-Purpan (CPTP), INSERM, CNRS, University of Toulouse, 31024 Toulouse, FranceCenter for Pathophysiology Toulouse-Purpan (CPTP), INSERM, CNRS, University of Toulouse, 31024 Toulouse, FranceCenter for Pathophysiology Toulouse-Purpan (CPTP), INSERM, CNRS, University of Toulouse, 31024 Toulouse, FranceDepartment of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USACenter for Pathophysiology Toulouse-Purpan (CPTP), INSERM, CNRS, University of Toulouse, 31024 Toulouse, France; Corresponding authorSummary: Control of CNS pathogens by CD8 T cells is key to avoid fatal neuroinflammation. Yet, the modalities of MHC I presentation in the brain are poorly understood. Here, we analyze the antigen presentation mechanisms underlying CD8 T cell-mediated control of the Toxoplasma gondii parasite in the CNS. We show that MHC I presentation of an efficiently processed model antigen (GRA6-OVA), even when not expressed in the bradyzoite stage, reduces cyst burden and dampens encephalitis in C57BL/6 mice. Antigen presentation assays with infected primary neurons reveal a correlation between lower MHC I presentation of tachyzoite antigens by neurons and poor parasite control in vivo. Using conditional MHC I-deficient mice, we find that neuronal MHC I presentation is required for robust restriction of T. gondii in the CNS during chronic phase, showing the importance of MHC I presentation by CNS neurons in the control of a prevalent brain pathogen. : Salvioni et al. uncover the modalities of antigen presentation in the mouse brain during chronic infection by the Toxoplasma gondii parasite. Parasite load and cerebral inflammation are reduced by efficient MHC I presentation of tachyzoite antigens. Neuronal MHC I presentation is critical for robust control of brain parasite. Keywords: neuroinflammation, encephalitis, brain infection, antigen presentation, neuron, CD8 T cell, Toxoplasma gondii, parasitehttp://www.sciencedirect.com/science/article/pii/S2211124719306801 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Anna Salvioni Marcy Belloy Aurore Lebourg Emilie Bassot Vincent Cantaloube-Ferrieu Virginie Vasseur Sophie Blanié Roland S. Liblau Elsa Suberbielle Ellen A. Robey Nicolas Blanchard |
spellingShingle |
Anna Salvioni Marcy Belloy Aurore Lebourg Emilie Bassot Vincent Cantaloube-Ferrieu Virginie Vasseur Sophie Blanié Roland S. Liblau Elsa Suberbielle Ellen A. Robey Nicolas Blanchard Robust Control of a Brain-Persisting Parasite through MHC I Presentation by Infected Neurons Cell Reports |
author_facet |
Anna Salvioni Marcy Belloy Aurore Lebourg Emilie Bassot Vincent Cantaloube-Ferrieu Virginie Vasseur Sophie Blanié Roland S. Liblau Elsa Suberbielle Ellen A. Robey Nicolas Blanchard |
author_sort |
Anna Salvioni |
title |
Robust Control of a Brain-Persisting Parasite through MHC I Presentation by Infected Neurons |
title_short |
Robust Control of a Brain-Persisting Parasite through MHC I Presentation by Infected Neurons |
title_full |
Robust Control of a Brain-Persisting Parasite through MHC I Presentation by Infected Neurons |
title_fullStr |
Robust Control of a Brain-Persisting Parasite through MHC I Presentation by Infected Neurons |
title_full_unstemmed |
Robust Control of a Brain-Persisting Parasite through MHC I Presentation by Infected Neurons |
title_sort |
robust control of a brain-persisting parasite through mhc i presentation by infected neurons |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2019-06-01 |
description |
Summary: Control of CNS pathogens by CD8 T cells is key to avoid fatal neuroinflammation. Yet, the modalities of MHC I presentation in the brain are poorly understood. Here, we analyze the antigen presentation mechanisms underlying CD8 T cell-mediated control of the Toxoplasma gondii parasite in the CNS. We show that MHC I presentation of an efficiently processed model antigen (GRA6-OVA), even when not expressed in the bradyzoite stage, reduces cyst burden and dampens encephalitis in C57BL/6 mice. Antigen presentation assays with infected primary neurons reveal a correlation between lower MHC I presentation of tachyzoite antigens by neurons and poor parasite control in vivo. Using conditional MHC I-deficient mice, we find that neuronal MHC I presentation is required for robust restriction of T. gondii in the CNS during chronic phase, showing the importance of MHC I presentation by CNS neurons in the control of a prevalent brain pathogen. : Salvioni et al. uncover the modalities of antigen presentation in the mouse brain during chronic infection by the Toxoplasma gondii parasite. Parasite load and cerebral inflammation are reduced by efficient MHC I presentation of tachyzoite antigens. Neuronal MHC I presentation is critical for robust control of brain parasite. Keywords: neuroinflammation, encephalitis, brain infection, antigen presentation, neuron, CD8 T cell, Toxoplasma gondii, parasite |
url |
http://www.sciencedirect.com/science/article/pii/S2211124719306801 |
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