{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T20:48:40Z","timestamp":1777927720223,"version":"3.51.4"},"update-to":[{"DOI":"10.1371\/journal.ppat.1011837","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,12,13]],"date-time":"2023-12-13T00:00:00Z","timestamp":1702425600000}}],"reference-count":50,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2023,11,29]],"date-time":"2023-11-29T00:00:00Z","timestamp":1701216000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["GRK1949"],"award-info":[{"award-number":["GRK1949"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["GRK1949"],"award-info":[{"award-number":["GRK1949"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["GRK1949"],"award-info":[{"award-number":["GRK1949"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Neuropilin-1 (Nrp-1) expression on CD8<jats:sup>+<\/jats:sup> T cells has been identified in tumor-infiltrating lymphocytes and in persistent murine gamma-herpes virus infections, where it interferes with the development of long-lived memory T cell responses. In parasitic and acute viral infections, the role of Nrp-1 expression on CD8<jats:sup>+<\/jats:sup> T cells remains unclear. Here, we demonstrate a strong induction of Nrp-1 expression on CD8<jats:sup>+<\/jats:sup> T cells in <jats:italic>Plasmodium berghei<\/jats:italic> ANKA (PbA)-infected mice that correlated with neurological deficits of experimental cerebral malaria (ECM). Likewise, the frequency of Nrp-1<jats:sup>+<\/jats:sup>CD8<jats:sup>+<\/jats:sup> T cells was significantly elevated and correlated with liver damage in the acute phase of lymphocytic choriomeningitis virus (LCMV) infection. Transcriptomic and flow cytometric analyses revealed a highly activated phenotype of Nrp-1<jats:sup>+<\/jats:sup>CD8<jats:sup>+<\/jats:sup> T cells from infected mice. Correspondingly, <jats:italic>in vitro<\/jats:italic> experiments showed rapid induction of Nrp-1 expression on CD8<jats:sup>+<\/jats:sup> T cells after stimulation in conjunction with increased expression of activation-associated molecules. Strikingly, T cell-specific Nrp-1 ablation resulted in reduced numbers of activated T cells in the brain of PbA-infected mice as well as in spleen and liver of LCMV-infected mice and alleviated the severity of ECM and LCMV-induced liver pathology. Mechanistically, we identified reduced blood-brain barrier leakage associated with reduced parasite sequestration in the brain of PbA-infected mice with T cell-specific Nrp-1 deficiency. In conclusion, Nrp-1 expression on CD8<jats:sup>+<\/jats:sup> T cells represents a very early activation marker that exacerbates deleterious CD8<jats:sup>+<\/jats:sup> T cell responses during both, parasitic PbA and acute LCMV infections.<\/jats:p>","DOI":"10.1371\/journal.ppat.1011837","type":"journal-article","created":{"date-parts":[[2023,11,29]],"date-time":"2023-11-29T18:44:06Z","timestamp":1701283446000},"page":"e1011837","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Neuropilin-1 identifies a subset of highly activated CD8+ T cells during parasitic and viral 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