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The T cell inhibitory molecule BTNL2 is upregulated in mild Plasmodium falciparum infection and is protective during experimental cerebral malaria

Title: The T cell inhibitory molecule BTNL2 is upregulated in mild Plasmodium falciparum infection and is protective during experimental cerebral malaria
Authors: Subramaniam, Krishanthi S.; Spaulding, Emily; Ivan, Emil; Mutimura, Eugene; Kim, Ryung S.; Liu, Xikui; Dong, Chen; Feintuch, Catherine M.; Zhang, Xingxing; Anastos, Kathryn; Lauvau, Gregoire; Daily, Johanna P.
Publisher Information: Oxford University Press
Publication Year: 2015
Collection: HighWire Press (Stanford University)
Subject Terms: MAJOR ARTICLE
Description: Plasmodium falciparum infection can result in severe disease which is associated with elevated inflammation and vital organ dysfunction; however malaria endemic residents gain protection from lethal outcomes and manifest only mild symptoms during infection. To characterize host responses associated with this more effective antimalarial response, we characterized whole blood transcriptional profiles in Rwandan adults during a mild malaria episode and compared them to a convalescence sample. We observed transcriptional upregulation in many pathways, including Type-I IFN, IFN-γ, complement activation and nitric oxide during malaria infection, which provide benchmarks of mild disease physiology. Transcripts encoding negative regulators of T cell activation such as programmed death ligand 1 (PD-L1), programmed cell death 1 ligand 2 (PD-L2) and the butyrophilin family member BTNL2 were also increased. To support an important functional role for BTNL2 during malaria infection, we studied chimeric mice reconstituted with BTNL2−/- or wild type (WT) hematopoietic cells that were inoculated with P. berghei ANKA, a murine model of cerebral malaria. We found that BTNL2−/- chimeric mice had a significant loss of survival than WT counterparts. Collectively these data characterize the immune responses associated with mild malaria and uncovers a novel role for BTNL2 in the host response to malaria.
Document Type: text
File Description: text/html
Language: English
Relation: http://jid.oxfordjournals.org/cgi/content/short/jiv217v1; http://dx.doi.org/10.1093/infdis/jiv217
DOI: 10.1093/infdis/jiv217
Availability: http://jid.oxfordjournals.org/cgi/content/short/jiv217v1; https://doi.org/10.1093/infdis/jiv217
Rights: Copyright (C) 2015, Infectious Diseases Society of America
Accession Number: edsbas.BAC8AC6D
Database: BASE