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

doi:10.1038/nature24994

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

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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 language	English
Journal	Nature
Volume	552
Issue number	7683
Pages (from-to)	101-105
Number of pages	5
ISSN	0028-0836
DOIs	https://doi.org/10.1038/nature24994
Publication status	Published - 7 Dec 2017

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Saito, F., Hirayasu, K., Satoh, T., Wang, C. W., Lusingu, J., Arimori, T., Shida, K., Palacpac, N. M. Q., Itagaki, S., Iwanaga, S., Takashima, E., Tsuboi, T., Kohyama, M., Suenaga, T., Colonna, M., Takagi, J., Lavstsen, T., Horii, T., & Arase, H. (2017). Immune evasion of Plasmodium falciparum by RIFIN via inhibitory receptors. Nature, 552(7683), 101-105. https://doi.org/10.1038/nature24994

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 2017, 'Immune evasion of Plasmodium falciparum by RIFIN via inhibitory receptors', Nature, vol. 552, no. 7683, pp. 101-105. https://doi.org/10.1038/nature24994

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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",

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AU - Saito, Fumiji

AU - Hirayasu, Kouyuki

AU - Satoh, Takeshi

AU - Wang, Christian W

AU - Lusingu, John

AU - Arimori, Takao

AU - Shida, Kyoko

AU - Palacpac, Nirianne Marie Q

AU - Itagaki, Sawako

AU - Iwanaga, Shiroh

AU - Takashima, Eizo

AU - Tsuboi, Takafumi

AU - Kohyama, Masako

AU - Suenaga, Tadahiro

AU - Colonna, Marco

AU - Takagi, Junichi

AU - Lavstsen, Thomas

AU - Horii, Toshihiro

AU - Arase, Hisashi

PY - 2017/12/7

Y1 - 2017/12/7

N2 - 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.

AB - 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.

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DO - 10.1038/nature24994

M3 - Letter

C2 - 29186116

SN - 0028-0836

VL - 552

SP - 101

EP - 105

JO - Nature

JF - Nature

IS - 7683

ER -

Immune evasion of Plasmodium falciparum by RIFIN via inhibitory receptors

Abstract

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