학술논문
Neuropilin-1 identifies a subset of highly activated CD8.sup.+ T cells during parasitic and viral infections
Research Article
cluster of differentiation 8
Research Article
cluster of differentiation 8
Document Type
Report
Author
Source
PLoS Pathogens. November 29, 2023, Vol. 19 Issue 11, e1011837
Subject
Language
English
ISSN
1553-7366
Abstract
Author(s): Hanna Abberger 1,2,3, Matthias Hose 1, Anne Ninnemann 1, Christopher Menne 4,5, Mareike Eilbrecht 6, Karl S. Lang 6, Kai Matuschewski 7, Robert Geffers 8, Josephine Herz 9,10, Jan [...]
Neuropilin-1 (Nrp-1) expression on CD8.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.sup.+ T cells remains unclear. Here, we demonstrate a strong induction of Nrp-1 expression on CD8.sup.+ T cells in Plasmodium berghei ANKA (PbA)-infected mice that correlated with neurological deficits of experimental cerebral malaria (ECM). Likewise, the frequency of Nrp-1.sup.+ CD8.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.sup.+ CD8.sup.+ T cells from infected mice. Correspondingly, in vitro experiments showed rapid induction of Nrp-1 expression on CD8.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.sup.+ T cells represents a very early activation marker that exacerbates deleterious CD8.sup.+ T cell responses during both, parasitic PbA and acute LCMV infections.
Neuropilin-1 (Nrp-1) expression on CD8.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.sup.+ T cells remains unclear. Here, we demonstrate a strong induction of Nrp-1 expression on CD8.sup.+ T cells in Plasmodium berghei ANKA (PbA)-infected mice that correlated with neurological deficits of experimental cerebral malaria (ECM). Likewise, the frequency of Nrp-1.sup.+ CD8.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.sup.+ CD8.sup.+ T cells from infected mice. Correspondingly, in vitro experiments showed rapid induction of Nrp-1 expression on CD8.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.sup.+ T cells represents a very early activation marker that exacerbates deleterious CD8.sup.+ T cell responses during both, parasitic PbA and acute LCMV infections.