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Robust Control of a Neurotropic Parasite Through MHC I Presentation by Infected Neurons

46 Pages Posted: 15 Sep 2018 Sneak Peek Status: Review Complete

See all articles by Anna Salvioni

Anna Salvioni

University of Toulouse 3, Paul Sabatier University - Center for Pathophysiology Toulouse-Purpan (CPTP)

Marcy Belloy

University of Toulouse 3, Paul Sabatier University - Center for Pathophysiology Toulouse-Purpan (CPTP)

Aurore Lebourg

University of Toulouse 3, Paul Sabatier University - Center for Pathophysiology Toulouse-Purpan (CPTP)

Emilie Bassot

University of Toulouse 3, Paul Sabatier University - Center for Pathophysiology Toulouse-Purpan (CPTP)

Vincent Cantaloube-Ferrieu

University of Toulouse 3, Paul Sabatier University - Center for Pathophysiology Toulouse-Purpan (CPTP)

Virginie Vasseur

University of Toulouse 3, Paul Sabatier University - Center for Pathophysiology Toulouse-Purpan (CPTP)

Sophie Blanié

University of Toulouse 3, Paul Sabatier University - Center for Pathophysiology Toulouse-Purpan (CPTP)

Roland S. Liblau

University of Toulouse 3, Paul Sabatier University - Center for Pathophysiology Toulouse-Purpan (CPTP)

Elsa Suberbielle

University of Toulouse 3, Paul Sabatier University - Center for Pathophysiology Toulouse-Purpan (CPTP)

Ellen A. Robey

University of California, Berkeley - Department of Molecular and Cell Biology

Nicolas Blanchard

University of Toulouse 3, Paul Sabatier University - Center for Pathophysiology Toulouse-Purpan (CPTP)

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Abstract

Inadequate immune control of Central Nervous System (CNS) pathogens may result in fatal neuroinflammation. CD8 T cells are instrumental for CNS pathogen control but the functions of brain-resident antigen-presenting cells remain poorly understood. Here, we analyzed the modalities of MHC I presentation of Toxoplasma gondii, a parasite chronically residing in the CNS. Using transgenic parasites with stage-restricted expression of a protective antigen, we show that MHC I presentation of the rapidly dividing tachyzoites prevents encephalitis and that improper parasite control during encephalitis correlates with sub-optimal MHC I presentation of T. gondii by neurons. Thanks to conditional MHC I-deficient mice, we demonstrate that neuronal MHC I presentation is dispensable for brain CD8 T cell accumulation but is required for durable pathogen control. Thus, MHC I presentation of parasite antigens by CNS neurons is a pivotal checkpoint that determines the clinical outcome of a prevalent and chronic brain infection.

Suggested Citation

Salvioni, Anna and Belloy, Marcy and Lebourg, Aurore and Bassot, Emilie and Cantaloube-Ferrieu, Vincent and Vasseur, Virginie and Blanié, Sophie and Liblau, Roland S. and Suberbielle, Elsa and Robey, Ellen A. and Blanchard, Nicolas, Robust Control of a Neurotropic Parasite Through MHC I Presentation by Infected Neurons (September 14, 2018). Available at SSRN: https://ssrn.com/abstract=3249820 or http://dx.doi.org/10.2139/ssrn.3249820
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Anna Salvioni (Contact Author)

University of Toulouse 3, Paul Sabatier University - Center for Pathophysiology Toulouse-Purpan (CPTP)

118 Route de Narbonne
Toulouse cedex 9, F-31062
France

Marcy Belloy

University of Toulouse 3, Paul Sabatier University - Center for Pathophysiology Toulouse-Purpan (CPTP)

118 Route de Narbonne
Toulouse cedex 9, F-31062
France

Aurore Lebourg

University of Toulouse 3, Paul Sabatier University - Center for Pathophysiology Toulouse-Purpan (CPTP)

118 Route de Narbonne
Toulouse cedex 9, F-31062
France

Emilie Bassot

University of Toulouse 3, Paul Sabatier University - Center for Pathophysiology Toulouse-Purpan (CPTP)

118 Route de Narbonne
Toulouse cedex 9, F-31062
France

Vincent Cantaloube-Ferrieu

University of Toulouse 3, Paul Sabatier University - Center for Pathophysiology Toulouse-Purpan (CPTP)

118 Route de Narbonne
Toulouse cedex 9, F-31062
France

Virginie Vasseur

University of Toulouse 3, Paul Sabatier University - Center for Pathophysiology Toulouse-Purpan (CPTP)

118 Route de Narbonne
Toulouse cedex 9, F-31062
France

Sophie Blanié

University of Toulouse 3, Paul Sabatier University - Center for Pathophysiology Toulouse-Purpan (CPTP)

118 Route de Narbonne
Toulouse cedex 9, F-31062
France

Roland S. Liblau

University of Toulouse 3, Paul Sabatier University - Center for Pathophysiology Toulouse-Purpan (CPTP)

118 Route de Narbonne
Toulouse cedex 9, F-31062
France

Elsa Suberbielle

University of Toulouse 3, Paul Sabatier University - Center for Pathophysiology Toulouse-Purpan (CPTP)

118 Route de Narbonne
Toulouse cedex 9, F-31062
France

Ellen A. Robey

University of California, Berkeley - Department of Molecular and Cell Biology

310 Barrows Hall
Berkeley, CA 94720
United States

Nicolas Blanchard

University of Toulouse 3, Paul Sabatier University - Center for Pathophysiology Toulouse-Purpan (CPTP) ( email )

118 Route de Narbonne
Toulouse cedex 9, F-31062
France

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