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

Krishanthi S. Subramaniam, Emily Spaulding, Emil Ivan, Eugene Mutimura, Ryung S. Kim, Xikui Liu, Chen Dong, Catherine M. Feintuch, Xingxing Zhang, Kathryn Anastos, Gregoire Lauvau, Johanna P. Daily

Research output: Contribution to journalArticle

7 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1322-1331
Number of pages10
JournalJournal of Infectious Diseases
Volume212
Issue number8
DOIs
StatePublished - Oct 15 2015

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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