Beschreibung:
<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>