IFNAR1 Controls Progression to Cerebral Malaria in Children and CD8+ T Cell Brain Pathology in Plasmodium berghei-Infected Mice

Ball, E. A.; Sambo, M. R.; Martins, M.; Trovoada, M. J.; Benchimol, C.; Costa, J.; Antunes Goncalves, L.; Coutinho, A.; Penha-Goncalves, C.

Publication

IFNAR1 Controls Progression to Cerebral Malaria in Children and CD8+ T Cell Brain Pathology in Plasmodium berghei-Infected Mice

2013-03-06Journal article

dc.contributor.author	Ball, E. A.
dc.contributor.author	Sambo, M. R.
dc.contributor.author	Martins, M.
dc.contributor.author	Trovoada, M. J.
dc.contributor.author	Benchimol, C.
dc.contributor.author	Costa, J.
dc.contributor.author	Antunes Goncalves, L.
dc.contributor.author	Coutinho, A.
dc.contributor.author	Penha-Goncalves, C.
dc.date.accessioned	2016-05-03T17:36:15Z
dc.date.available	2016-05-03T17:36:15Z
dc.date.issued	2013-03-06
dc.description	This publication hasn't any creative commons license associated. There is no public supplementary material available.
dc.description.abstract	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.	pt_PT
dc.description.sponsorship	FCT fellowships: (SFRH/BD/33564/2008, SFRH/BPD/29354/2006).	pt_PT
dc.identifier.citation	Ball, 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.	pt_PT
dc.identifier.doi	10.4049/jimmunol.1300114	pt_PT
dc.identifier.uri	http://hdl.handle.net/10400.7/592
dc.language.iso	eng	pt_PT
dc.peerreviewed	yes	pt_PT
dc.publisher	The American Association of Immunologists	pt_PT
dc.relation.publisherversion	http://www.jimmunol.org/content/190/10/5118.abstract?sid=29bee24e-8292-4aeb-9abf-b34c8d7e95d7	pt_PT
dc.rights.uri	http://creativecommons.org/licenses/by/4.0/	pt_PT
dc.subject	CD8+ T cells	pt_PT
dc.subject	Cerebral malaria	pt_PT
dc.subject	Experimental Cerebral malaria	pt_PT
dc.subject	Genetic association	pt_PT
dc.subject	IFNAR1	pt_PT
dc.title	IFNAR1 Controls Progression to Cerebral Malaria in Children and CD8+ T Cell Brain Pathology in Plasmodium berghei-Infected Mice	pt_PT
dc.type	journal article
dspace.entity.type	Publication
oaire.citation.endPage	5127	pt_PT
oaire.citation.issue	10	pt_PT
oaire.citation.startPage	5118	pt_PT
oaire.citation.title	The Journal of Immunology	pt_PT
oaire.citation.volume	190	pt_PT
rcaap.rights	openAccess	pt_PT
rcaap.type	article	pt_PT