@article{59d41731268d44d2ad85c090b6ca9080,
title = "Immune evasion of Plasmodium falciparum by RIFIN via inhibitory receptors",
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.",
author = "Fumiji Saito and Kouyuki Hirayasu and Takeshi Satoh and Wang, {Christian W.} and John Lusingu and Takao Arimori and Kyoko Shida and Palacpac, {Nirianne Marie Q.} and Sawako Itagaki and Shiroh Iwanaga and Eizo Takashima and Takafumi Tsuboi and Masako Kohyama and Tadahiro Suenaga and Marco Colonna and Junichi Takagi and Thomas Lavstsen and Toshihiro Horii and Hisashi Arase",
note = "Funding Information: We thank T. Mitamura for discussions, K. Saito for mass spectrometry analysis, M. Matsumoto and S. Matsuoka for technical assistance, the Thai and Tanzanian donors and the Japanese Red Cross Society for providing human erythrocytes and human plasma. This work was partly supported by the Japanese Initiative for Progress of Research on Infectious Disease for Global Epidemic from the Japan Agency for Medical Research and Development (AMED) (H.A.), the Platform Project for Supporting Drug Discovery and Life Science Research from AMED (J.T.), JSPS KAKENHI grant numbers JP16K08839 (K.H.), JP16H05195 (T.Su.), JP15K08531 (M.K.), MEXT KAKENHI grant numbers JP26117714 (H.A.), JP23117008 (T.T.), JP24115005 (H.A.), the Senri Life Science Foundation (K.H.), the Kato Memorial Bioscience Foundation (K.H.), the Danish Council for Independent Research grants 1333-00220 (C.W.W.) and 4004-00624B (T.L.), The Lundbeck Foundation (T.L.) and the United States National Institutes of Health (NIH R01HL130678, T.L.). F.S was supported by the Taniguchi Memorial Fellowship program. Funding Information: Acknowledgements We thank T. Mitamura for discussions, K. Saito for mass spectrometry analysis, M. Matsumoto and S. Matsuoka for technical assistance, the Thai and Tanzanian donors and the Japanese Red Cross Society for providing human erythrocytes and human plasma. This work was partly supported by the Japanese Initiative for Progress of Research on Infectious Disease for Global Epidemic from the Japan Agency for Medical Research and Development (AMED) (H.A.), the Platform Project for Supporting Drug Discovery and Life Science Research from AMED (J.T.), JSPS KAKENHI grant numbers JP16K08839 (K.H.), JP16H05195 (T.Su.), JP15K08531 (M.K.), MEXT KAKENHI grant numbers JP26117714 (H.A.), JP23117008 (T.T.), JP24115005 (H.A.), the Senri Life Science Foundation (K.H.), the Kato Memorial Bioscience Foundation (K.H.), the Danish Council for Independent Research grants Publisher Copyright: {\textcopyright} 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.",
year = "2017",
doi = "10.1038/nature24994",
language = "English",
volume = "552",
pages = "101--105",
journal = "Nature",
issn = "0028-0836",
number = "7683",
}