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J Infect Dis. 2015 Oct 15;212(8):1322-31. doi: 10.1093/infdis/jiv217. Epub 2015 Apr 15.

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

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Departments of Microbiology and Immunology.
Department of Biomedical Laboratory Sciences, College of Medicine and Health Sciences, University of Rwanda.
Regional Alliance for Sustainable Development, Kigali.
Epidemiology and Population Health.
Department of Immunology, University of Texas MD Anderson Cancer Center, Houston.
Medicine, Albert Einstein College of Medicine, Bronx, New York.
Departments of Microbiology and Immunology Medicine, Albert Einstein College of Medicine, Bronx, New York.


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.


BTNL2; Plasmodium berghei; Plasmodium falciparum; Rwanda HIV; antibody responses; atypical memory B cells; experimental cerebral malaria; immune response; malaria; mild malaria; mouse model

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