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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2024,6,11]]},"abstract":"<jats:p>\n                    Chronic\n                    <jats:italic>Toxoplasma gondii<\/jats:italic>\n                    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\n                    <jats:italic>T. gondii<\/jats:italic>\n                    leading to effective CD8+ T cell\u2013mediated 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\u2013specific 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\u2013dependent 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\n                    <jats:italic>T. gondii<\/jats:italic>\n                    latent infection and which differentiation is shaped by neuronal and microglial MHC I presentation. A more detailed understanding of local T cell\u2013mediated immune surveillance of this common parasite is needed for harnessing brain-resident CD8+ T cells in order to enhance control of chronic brain infections.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2403054121","type":"journal-article","created":{"date-parts":[[2024,6,5]],"date-time":"2024-06-05T13:39:42Z","timestamp":1717594782000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":24,"title":["Protective function and differentiation cues of brain-resident CD8+ T cells during surveillance of latent\n                    <i>Toxoplasma gondii<\/i>\n                    infection"],"prefix":"10.1073","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8311-0202","authenticated-orcid":false,"given":"R\u00e9mi","family":"Porte","sequence":"first","affiliation":[{"name":"Toulouse Institute for Infectious and Inflammatory Diseases, Infinity, Inserm, CNRS, University of Toulouse, Toulouse 31300, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcy","family":"Belloy","sequence":"additional","affiliation":[{"name":"Toulouse Institute for Infectious and Inflammatory Diseases, Infinity, Inserm, CNRS, University of Toulouse, Toulouse 31300, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5099-958X","authenticated-orcid":false,"given":"Alexis","family":"Audibert","sequence":"additional","affiliation":[{"name":"Toulouse Institute for Infectious and Inflammatory Diseases, Infinity, Inserm, CNRS, University of Toulouse, Toulouse 31300, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8646-5290","authenticated-orcid":false,"given":"Emilie","family":"Bassot","sequence":"additional","affiliation":[{"name":"Toulouse Institute for Infectious and Inflammatory Diseases, Infinity, Inserm, CNRS, University of Toulouse, Toulouse 31300, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4997-8937","authenticated-orcid":false,"given":"Amel","family":"A\u00efda","sequence":"additional","affiliation":[{"name":"Toulouse Institute for Infectious and Inflammatory Diseases, Infinity, Inserm, CNRS, University of Toulouse, Toulouse 31300, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marine","family":"Alis","sequence":"additional","affiliation":[{"name":"Toulouse Institute for Infectious and Inflammatory Diseases, Infinity, Inserm, CNRS, University of Toulouse, Toulouse 31300, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4324-9127","authenticated-orcid":false,"given":"Romain","family":"Miranda-Capet","sequence":"additional","affiliation":[{"name":"Toulouse Institute for Infectious and Inflammatory Diseases, Infinity, Inserm, CNRS, University of Toulouse, Toulouse 31300, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aur\u00e9lie","family":"Jourdes","sequence":"additional","affiliation":[{"name":"Toulouse Institute for Infectious and Inflammatory Diseases, Infinity, Inserm, CNRS, University of Toulouse, Toulouse 31300, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaas P. 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