Immune evasion of Plasmodium falciparum by RIFIN via inhibitory receptors

Fumiji Saito, Kouyuki Hirayasu, Takeshi Satoh, Christian W. Wang, John Lusingu, Takao Arimori, Kyoko Shida, Nirianne Marie Q. Palacpac, Sawako Itagaki, Shiroh Iwanaga, Eizo Takashima, Takafumi Tsuboi, Masako Kohyama, Tadahiro Suenaga, Marco Colonna, Junichi Takagi, Thomas Lavstsen, Toshihiro Horii, Hisashi Arase

Research output: Contribution to journalArticlepeer-review

65 Scopus citations

Abstract

Malaria is among the most serious infectious diseases affecting humans, accounting for approximately half a million deaths each year1. Plasmodium falciparum causes most life-threatening cases of malaria. Acquired immunity to malaria is inefficient, even after repeated exposure to P. falciparum2, 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 genome3 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.

Original languageEnglish
Pages (from-to)101-105
Number of pages5
JournalNature
Volume552
Issue number7683
DOIs
StatePublished - 2017

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