Neuropilin-1 identifies a subset of highly activated CD8+ T cells during parasitic and viral infections.
Hanna Abberger, Matthias Hose, Anne Ninnemann, Christopher Menne, Mareike Eilbrecht, Karl S Lang, Kai Matuschewski, Robert Geffers, Josephine Herz, Jan Buer, Astrid M Westendorf, Wiebke Hansen
Author Information
Hanna Abberger: Institute of Medical Microbiology, University Hospital Essen, University Duisburg-Essen, Germany.
Matthias Hose: Institute of Medical Microbiology, University Hospital Essen, University Duisburg-Essen, Germany.
Anne Ninnemann: Institute of Medical Microbiology, University Hospital Essen, University Duisburg-Essen, Germany.
Christopher Menne: Institute of Virology, University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Germany.
Mareike Eilbrecht: Institute of Immunology, University Hospital Essen, University Duisburg-Essen, Germany.
Karl S Lang: Institute of Immunology, University Hospital Essen, University Duisburg-Essen, Germany.
Kai Matuschewski: Department of Molecular Parasitology, Institute of Biology, Humboldt University Berlin, Germany.
Robert Geffers: Genome Analytics, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Josephine Herz: Department of Pediatrics 1, Neonatology & Experimental perinatal Neurosciences, University Hospital Essen, University Duisburg-Essen, Germany.
Jan Buer: Institute of Medical Microbiology, University Hospital Essen, University Duisburg-Essen, Germany.
Astrid M Westendorf: Institute of Medical Microbiology, University Hospital Essen, University Duisburg-Essen, Germany.
Wiebke Hansen: Institute of Medical Microbiology, University Hospital Essen, University Duisburg-Essen, Germany.
Neuropilin-1 (Nrp-1) expression on CD8+ 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+ T cells remains unclear. Here, we demonstrate a strong induction of Nrp-1 expression on CD8+ 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+CD8+ 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+CD8+ T cells from infected mice. Correspondingly, in vitro experiments showed rapid induction of Nrp-1 expression on CD8+ 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+ T cells represents a very early activation marker that exacerbates deleterious CD8+ T cell responses during both, parasitic PbA and acute LCMV infections.
References
Proc Natl Acad Sci U S A. 2011 Feb 1;108(5):2040-5
[PMID: 21245328]
Front Immunol. 2018 Nov 13;9:2611
[PMID: 30483269]
