Journal
JOURNAL OF INFECTIOUS DISEASES
Volume 212, Issue 8, Pages 1322-1331Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiv217
Keywords
Plasmodium falciparum; mild malaria; immune response; BTNL2; Plasmodium berghei; mouse model; experimental cerebral malaria; Rwanda HIV; malaria; antibody responses; atypical memory B cells
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Funding
- National Institutes of Health [1RC1AI086224]
- Albert Einstein Global Health Center
- National Institute of Allergy and Infectious Disease [NIH-NIAID T32 AI046985]
- NIH-NIAID [T32 AI070117]
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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., 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.
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