title: The T-Cell Inhibitory Molecule Butyrophilin-Like 2 Is Up-regulated in Mild Plasmodium falciparum Infection and Is Protective During Experimental Cerebral Malaria.
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.
authors.affiliation: Departments of Microbiology and Immunology.
authors.forename: Krishanthi S
authors.initials: KS
authors.lastname: Subramaniam
authors.affiliation: Departments of Microbiology and Immunology.
authors.forename: Emily
authors.initials: E
authors.lastname: Spaulding
authors.affiliation: Department of Biomedical Laboratory Sciences, College of Medicine and Health Sciences, University of Rwanda.
authors.forename: Emil
authors.initials: E
authors.lastname: Ivan
authors.affiliation: Regional Alliance for Sustainable Development, Kigali.
authors.forename: Eugene
authors.initials: E
authors.lastname: Mutimura
authors.affiliation: Epidemiology and Population Health.
authors.forename: Ryung S
authors.initials: RS
authors.lastname: Kim
authors.affiliation: Department of Immunology, University of Texas MD Anderson Cancer Center, Houston.
authors.forename: Xikui
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Immunology, University of Texas MD Anderson Cancer Center, Houston.
authors.forename: Chen
authors.initials: C
authors.lastname: Dong
authors.affiliation: Departments of Microbiology and Immunology.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Feintuch
authors.affiliation: Departments of Microbiology and Immunology.
authors.forename: Xingxing
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Medicine, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Anastos
authors.affiliation: Departments of Microbiology and Immunology.
authors.forename: Gregoire
authors.initials: G
authors.lastname: Lauvau
authors.affiliation: Departments of Microbiology and Immunology Medicine, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Johanna P
authors.initials: JP
authors.lastname: Daily
mesh_terms: D000328:Adult; D000818:Animals; D060890:B7-H1 Antigen / Q000276:immunology; D000071797:Butyrophilins; D003167:Complement Activation; D019353:Endemic Diseases; D005260:Female; D006801:Humans; D007370:Interferon Type I / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D008213:Lymphocyte Activation; D008288:Malaria / Q000453:epidemiology / Q000276:immunology / Q000469:parasitology; D016779:Malaria, Cerebral / Q000453:epidemiology / Q000276:immunology* / Q000469:parasitology; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000276:immunology* / Q000469:parasitology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000378:metabolism; D010962:Plasmodium berghei / Q000276:immunology; D010963:Plasmodium falciparum / Q000276:immunology*; D012432:Rwanda / Q000453:epidemiology; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D060890:B7-H1 Antigen; D000071797:Butyrophilins; D007370:Interferon Type I; D008562:Membrane Glycoproteins; D009569:Nitric Oxide; D007371:Interferon-gamma
keywords: BTNL2; Plasmodium berghei; Plasmodium falciparum; Rwanda HIV; antibody responses; atypical memory B cells; experimental cerebral malaria; immune response; malaria; mild malaria; mouse model