RRC ID 50089
Author Saito F, Hirayasu K, Satoh T, Wang CW, Lusingu J, Arimori T, Shida K, Palacpac NMQ, Itagaki S, Iwanaga S, Takashima E, Tsuboi T, Kohyama M, Suenaga T, Colonna M, Takagi J, Lavstsen T, Horii T, Arase H.
Title Immune evasion of Plasmodium falciparum by RIFIN via inhibitory receptors.
Journal Nature
Abstract Malaria is among the most serious infectious diseases affecting humans, accounting for approximately half a million deaths each year. Plasmodium falciparum causes most life-threatening cases of malaria. Acquired immunity to malaria is inefficient, even after repeated exposure to P. falciparum, but the immune regulatory mechanisms used by P. falciparum remain largely unknown. Here we show that P. falciparum uses immune inhibitory receptors to achieve immune evasion. RIFIN proteins are products of a polymorphic multigene family comprising approximately 150-200 genes per parasite genome that are expressed on the surface of infected erythrocytes. We found that a subset of RIFINs binds to either leucocyte immunoglobulin-like receptor B1 (LILRB1) or leucocyte-associated immunoglobulin-like receptor 1 (LAIR1). LILRB1-binding RIFINs inhibit activation of LILRB1-expressing B cells and natural killer (NK) cells. Furthermore, P. falciparum-infected erythrocytes isolated from patients with severe malaria were more likely to interact with LILRB1 than erythrocytes from patients with non-severe malaria, although an extended study with larger sample sizes is required to confirm this finding. Our results suggest that P. falciparum has acquired multiple RIFINs to evade the host immune system by targeting immune inhibitory receptors.
Volume 552(7683)
Pages 101-105
Published 2017-12-7
DOI 10.1038/nature24994
PII nature24994
PMID 29186116
PMC PMC5748893
MeSH Amino Acid Sequence Animals B-Lymphocytes / immunology B-Lymphocytes / metabolism CHO Cells Cricetulus Erythrocytes / immunology Erythrocytes / parasitology HEK293 Cells Humans Immune Evasion / immunology* Killer Cells, Natural / immunology Killer Cells, Natural / metabolism Leukocyte Immunoglobulin-like Receptor B1 / chemistry Leukocyte Immunoglobulin-like Receptor B1 / immunology* Ligands Malaria, Falciparum / immunology Malaria, Falciparum / parasitology Malaria, Falciparum / pathology Membrane Proteins / genetics Membrane Proteins / immunology* Membrane Proteins / metabolism Plasmodium falciparum / genetics Plasmodium falciparum / immunology* Plasmodium falciparum / metabolism Protozoan Proteins / genetics Protozoan Proteins / immunology* Protozoan Proteins / metabolism Receptors, Immunologic / chemistry Receptors, Immunologic / immunology* Sample Size
IF 42.779
Times Cited 35
Human and Animal Cells 293T(RCB2202) CHO-K1(RCB0285)