Protective function and differentiation cues of brain-resident CD8+ T cells during surveillance of latent Toxoplasma gondii infection.

Autor:	Porte R; Toulouse Institute for Infectious and Inflammatory Diseases, Infinity, Inserm, CNRS, University of Toulouse, Toulouse 31300, France., Belloy M; Toulouse Institute for Infectious and Inflammatory Diseases, Infinity, Inserm, CNRS, University of Toulouse, Toulouse 31300, France., Audibert A; Toulouse Institute for Infectious and Inflammatory Diseases, Infinity, Inserm, CNRS, University of Toulouse, Toulouse 31300, France., Bassot E; Toulouse Institute for Infectious and Inflammatory Diseases, Infinity, Inserm, CNRS, University of Toulouse, Toulouse 31300, France., Aïda A; Toulouse Institute for Infectious and Inflammatory Diseases, Infinity, Inserm, CNRS, University of Toulouse, Toulouse 31300, France., Alis M; Toulouse Institute for Infectious and Inflammatory Diseases, Infinity, Inserm, CNRS, University of Toulouse, Toulouse 31300, France., Miranda-Capet R; Toulouse Institute for Infectious and Inflammatory Diseases, Infinity, Inserm, CNRS, University of Toulouse, Toulouse 31300, France., Jourdes A; Toulouse Institute for Infectious and Inflammatory Diseases, Infinity, Inserm, CNRS, University of Toulouse, Toulouse 31300, France., van Gisbergen KPJM; Physiology and Cancer Programme, Champalimaud Research, Champalimaud Foundation, Lisbon 1400-038, Portugal., Masson F; Toulouse Institute for Infectious and Inflammatory Diseases, Infinity, Inserm, CNRS, University of Toulouse, Toulouse 31300, France., Blanchard N; Toulouse Institute for Infectious and Inflammatory Diseases, Infinity, Inserm, CNRS, University of Toulouse, Toulouse 31300, France.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2024 Jun 11; Vol. 121 (24), pp. e2403054121. Date of Electronic Publication: 2024 Jun 05.
DOI:	10.1073/pnas.2403054121
Abstrakt:	Chronic Toxoplasma gondii 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 T. gondii 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 T. gondii 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. Competing Interests: Competing interests statement:The authors declare no competing interest.
Databáze:	MEDLINE
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