The T-Cell Inhibitory Molecule Butyrophilin-Like 2 Is Up-regulated in Mild Plasmodium falciparum Infection and Is Protective During Experimental Cerebral Malaria

Subramaniam, Krishanthi, Spaulding, Emily, Ivan, Emil, Mutimura, Eugene, Kim, Ryung S, Liu, Xikui, Dong, Chen, Feintuch, Catherine, Zhang, Xingxing, Anastos, Kathryn, Lauvau, Gregoire and Daily, Johanna (2015) 'The T-Cell Inhibitory Molecule Butyrophilin-Like 2 Is Up-regulated in Mild Plasmodium falciparum Infection and Is Protective During Experimental Cerebral Malaria'. Journal of Infectious Disease, Vol 212, Issue 8, pp. 1322-1331.

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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.

Item Type:	Article
Uncontrolled Keywords:	NOT_LSTM
Subjects:	QW Microbiology and Immunology > Immune Responses > QW 700 Infection. Mechanisms of infection and resistance. QX Parasitology > Protozoa > QX 135 Plasmodia WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
Faculty: Department:	Biological Sciences > Vector Biology Department
Digital Object Identifer (DOI):	https://doi.org/10.1093/infdis/jiv217
Depositing User:	Jessica Jones
Date Deposited:	10 Feb 2016 14:40
Last Modified:	05 Nov 2024 12:46
URI:	https://archive.lstmed.ac.uk/id/eprint/5642

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