Immune evasion of Plasmodium falciparum by RIFIN via inhibitory receptors

• Published in: Nature (London) 2017-12, Vol.552 (7683), p.101-105
• Main Authors: Saito, Fumiji, Hirayasu, Kouyuki, Satoh, Takeshi, Wang, Christian W., Lusingu, John, Arimori, Takao, Shida, Kyoko, Palacpac, Nirianne Marie Q., Itagaki, Sawako, Iwanaga, Shiroh, Takashima, Eizo, Tsuboi, Takafumi, Kohyama, Masako, Suenaga, Tadahiro, Colonna, Marco, Takagi, Junichi, Lavstsen, Thomas, Horii, Toshihiro, Arase, Hisashi
• Format: Article
• Language: English
• Subjects: 13/31; 14/35; 42/109; 631/250/2161; 631/326/417/2547; 692/699/255/1629; 82/58; Binding proteins; Cell activation; Cell cycle; Erythrocytes; Gene expression; Genomes; Health aspects; Humanities and Social Sciences; Immune evasion; Immune response; Immune system; Immunity; Immunoglobulins; Infectious diseases; letter; Ligands; Lymphocytes B; Malaria; multidisciplinary; Natural killer cells; Observations; Parasites; Patients; Plasmodium falciparum; Proteins; Receptors; Regulatory mechanisms (biology); Science; Vector-borne diseases
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature24994

Proteins expressed on the surfaces of erythrocytes infected with Plasmodium falciparum help the parasite to evade the host immune system by acting as ligands for immune inhibitory receptors and thereby downregulating the immune response. Plasmodium immune evasion The malaria parasite, Plasmodium falciparum , uses several strategies to evade the host immune system during infection. Here, the authors report that a subset of parasite-derived ligands from the RIFIN protein family, which are expressed on the surface of infected red blood cells (erythrocytes), engage the immune inhibitory receptors leucocyte immunoglobulin-like receptor B1 (LILRB1) or leucocyte-associated immunoglobulin-like receptor 1 (LAIR1), which leads to the downregulation of immune responses. Malaria is among the most serious infectious diseases affecting humans, accounting for approximately half a million deaths each year 1 . Plasmodium falciparum causes most life-threatening cases of malaria. Acquired immunity to malaria is inefficient, even after repeated exposure to P. falciparum 2 , 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 3 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.