• Audibert, Alexis
• Bassot, Emilie
• Gisbergen, Klaas P. J. M. Van
• Jourdes, Aurélie
• Aïda, Amel
• Porte, Rémi
• Miranda-Capet, Romain
• Belloy, Marcy
• Blanchard, Nicolas
• Alis, Marine

Abstract

<jats:p>Chronic<jats:italic>Toxoplasma gondii</jats:italic>infection induces brain-resident CD8+ T cells (bTr), but the protective functions and differentiation cues of these cells remain undefined. Here, we used a mouse model of latent infection by<jats:italic>T. gondii</jats:italic>leading to effective CD8+ T cell–mediated parasite control. Thanks to antibody depletion approaches, we found that peripheral circulating CD8+ T cells are dispensable for brain parasite control during chronic stage, indicating that CD8+ bTr are able to prevent brain parasite reactivation. We observed that the retention markers CD69, CD49a, and CD103 are sequentially acquired by brain parasite–specific CD8+ T cells throughout infection and that a majority of CD69/CD49a/CD103 triple-positive (TP) CD8+ T cells also express Hobit, a transcription factor associated with tissue residency. This TP subset develops in a CD4+ T cell–dependent manner and is associated with effective parasite control during chronic stage. Conditional invalidation of Transporter associated with Antigen Processing (TAP)-mediated major histocompatibility complex (MHC) class I presentation showed that presentation of parasite antigens by glutamatergic neurons and microglia regulates the differentiation of CD8+ bTr into TP cells. Single-cell transcriptomic analyses revealed that resistance to encephalitis is associated with the expansion of stem-like subsets of CD8+ bTr. In summary, parasite-specific brain-resident CD8+ T cells are a functionally heterogeneous compartment which autonomously ensure parasite control during<jats:italic>T. gondii</jats:italic>latent infection and which differentiation is shaped by neuronal and microglial MHC I presentation. A more detailed understanding of local T cell–mediated immune surveillance of this common parasite is needed for harnessing brain-resident CD8+ T cells in order to enhance control of chronic brain infections.</jats:p>

Topics

• impedance spectroscopy