Ball, E. A.Sambo, M. R.Martins, M.Trovoada, M. J.Benchimol, C.Costa, J.Antunes Goncalves, L.Coutinho, A.Penha-Goncalves, C.2016-05-032016-05-032013-03-06Ball, E. A., Sambo, M. R., Martins, M., Trovoada, M. J., Benchimol, C., Costa, J., Antunes Goncalves, L., Coutinho, A., Penha-Goncalves, C. (2013). IFNAR1 Controls Progression to Cerebral Malaria in Children and CD8+ T Cell Brain Pathology in Plasmodium berghei-Infected Mice. The Journal of Immunology, 190(10), 5118–5127.http://hdl.handle.net/10400.7/592This publication hasn't any creative commons license associated. There is no public supplementary material available.Development of cerebral malaria (CM), a severe and fatal form of clinical Plasmodium falciparum infection, results from a damaging cascade of vascular, inflammatory, and immunological host responses that leads to brain injury. Progression to CM can be modified by host genetic factors. Our case-control study in Angolan children aimed at highlighting the role of IFN (α, β) receptor 1 (IFNAR1) in progression to CM. We report a robust association between IFNAR1 and CM protection, as well as detailed studies showing analogous protection from experimental CM in Ifnar1(-/-) mice infected with P. berghei ANKA. We developed a novel cell-transfer protocol that enables spleen cell priming in the absence of disease. This led to the discovery that IFNAR1 expression in CD8(+) T cells is crucial and can abrogate resistance to experimental CM in Ifnar1(-/-) mice. Splenic CD8(+) T cells from Ifnar1(-/-) mice are functionally activated upon infection, yet are unable to mediate experimental CM development within the brain tissue. Our findings prove that IFNAR1 signaling unleashes CD8(+) T cell effector capacity, which is vital for CM, and raises the hypothesis that the cohesive role of IFNAR1 in both human and mouse CM operates through CD8(+) T cell triggering.engCD8+ T cellsCerebral malariaExperimental Cerebral malariaGenetic associationIFNAR1journal article10.4049/jimmunol.1300114