TY - JOUR
T1 - The T-cell inhibitory molecule butyrophilin-like 2 is up-regulated in mild plasmodium falciparum infection and is protective during experimental cerebral malaria
AU - Subramaniam, Krishanthi S.
AU - Spaulding, Emily
AU - Ivan, Emil
AU - Mutimura, Eugene
AU - Kim, Ryung S.
AU - Liu, Xikui
AU - Dong, Chen
AU - Feintuch, Catherine M.
AU - Zhang, Xingxing
AU - Anastos, Kathryn
AU - Lauvau, Gregoire
AU - Daily, Johanna P.
N1 - Publisher Copyright:
© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.
PY - 2015/10/15
Y1 - 2015/10/15
N2 - 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.
AB - 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.
KW - BTNL2
KW - Plasmodium berghei
KW - Plasmodium falciparum
KW - Rwanda HIV
KW - antibody responses
KW - atypical memory B cells
KW - experimental cerebral malaria
KW - immune response
KW - malaria
KW - mild malaria
KW - mouse model
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U2 - 10.1093/infdis/jiv217
DO - 10.1093/infdis/jiv217
M3 - Article
C2 - 25883389
AN - SCOPUS:84943388606
SN - 0022-1899
VL - 212
SP - 1322
EP - 1331
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 8
ER -