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

Cell Rep. 2019 Jun 11;27(11):3254-3268.e8. doi: 10.1016/j.celrep.2019.05.051.


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.

Keywords: CD8 T cell; Toxoplasma gondii; antigen presentation; brain infection; encephalitis; neuroinflammation; neuron; parasite.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Protozoan / immunology*
  • Antigens, Protozoan / immunology
  • Brain / cytology
  • Brain / immunology*
  • Brain / parasitology
  • Cell Line
  • Cells, Cultured
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / immunology*
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neurons / immunology
  • Neurons / parasitology
  • Protozoan Proteins / immunology
  • Toxoplasma / immunology
  • Toxoplasma / pathogenicity
  • Toxoplasmosis, Cerebral / immunology*


  • Antibodies, Protozoan
  • Antigens, Protozoan
  • GRA6 protein, Toxoplasma gondii
  • Histocompatibility Antigens Class I
  • Protozoan Proteins