Robust Control of a Brain-Persisting Parasite through MHC I Presentation by Infected Neurons

Abstract

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