The T-Cell Inhibitory Molecule Butyrophilin-Like 2 Is Up-regulated in Mild Plasmodium falciparum Infection and Is Protective During Experimental Cerebral Malaria. (15th April 2015)

• Record Type: Journal Article
• 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.
• Is Part Of: Journal of infectious diseases. Volume 212:Number 8(2015:Oct. 15)
• Page Start: 1322
• Page End: 1331
• Publication Date: 2015-04-15
• Subjects: Plasmodium falciparum -- mild malaria -- immune response -- BTNL2 -- Plasmodium berghei -- mouse model -- experimental cerebral malaria -- Rwanda HIV -- malaria -- antibody responses -- atypical memory B cells; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jiv217
• Languages: English
• ISSNs: 0022-1899

Abstract

Abstract: Plasmodium falciparum infection can result in severe disease that 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 with findings from a convalescence sample. We observed transcriptional up-regulation in many pathways, including type I interferon, interferon 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 death 1 ligand 2 (PD-L2), and the butyrophilin family member butyrophilin-like 2 (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 hematopoietic cells that were inoculated with Plasmodium berghei ANKA, a murine model of cerebral malaria. We found that BTNL2 −/− chimeric mice had a significant decrease in survival compared with wild-type counterparts. Collectively these data characterize the immune responses associated with mild malaria and uncover a novel role for BTNL2 in the host response to malaria.