The T-cell inhibitory molecule butyrophilin-like 2 is up-regulated in mild plasmodium falciparum infection and is protective during experimental cerebral malaria

  • Subramaniam K
  • Spaulding E
  • Ivan E
 et al. 
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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 gamma, 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.

Author-supplied keywords

  • 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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  • Krishanthi S. Subramaniam

  • Emily Spaulding

  • Emil Ivan

  • Eugene Mutimura

  • Ryung S. Kim

  • Xikui Liu

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