<named-content content-type="genus-species">Plasmodium yoelii</named-content> Erythrocyte-Binding-like Protein Modulates Host Cell Membrane Structure, Immunity, and Disease Severity

ABSTRACT Erythrocyte-binding-like (EBL) proteins are known to play an important role in malaria parasite invasion of red blood cells (RBCs); however, any roles of EBL proteins in regulating host immune responses remain unknown. Here, we show that Plasmodium yoelii EBL (PyEBL) can shape disease sever...

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Autores principales:	Yu-chih Peng, Yanwei Qi, Cui Zhang, Xiangyu Yao, Jian Wu, Sittiporn Pattaradilokrat, Lu Xia, Keyla C. Tumas, Xiao He, Takahiro Ishizaki, Chen-Feng Qi, Anthony A. Holder, Timothy G. Myers, Carole A. Long, Osamu Kaneko, Jian Li, Xin-zhuan Su
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	Plasmodium mouse erythrocyte-binding-like EBL interferon pathogen-host interaction Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/5f2b539ed3854aa99666af61979e8b83
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spelling	oai:doaj.org-article:5f2b539ed3854aa99666af61979e8b832021-11-15T15:56:57Z<named-content content-type="genus-species">Plasmodium yoelii</named-content> Erythrocyte-Binding-like Protein Modulates Host Cell Membrane Structure, Immunity, and Disease Severity10.1128/mBio.02995-192150-7511https://doaj.org/article/5f2b539ed3854aa99666af61979e8b832020-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02995-19https://doaj.org/toc/2150-7511ABSTRACT Erythrocyte-binding-like (EBL) proteins are known to play an important role in malaria parasite invasion of red blood cells (RBCs); however, any roles of EBL proteins in regulating host immune responses remain unknown. Here, we show that Plasmodium yoelii EBL (PyEBL) can shape disease severity by modulating the surface structure of infected RBCs (iRBCs) and host immune responses. We identified an amino acid substitution (a change of C to Y at position 741 [C741Y]) in the protein trafficking domain of PyEBL between isogenic P. yoellii nigeriensis strain N67 and N67C parasites that produce different disease phenotypes in C57BL/6 mice. Exchanges of the C741Y alleles altered parasite growth and host survival accordingly. The C741Y substitution also changed protein processing and trafficking in merozoites and in the cytoplasm of iRBCs, reduced PyEBL binding to band 3, increased phosphatidylserine (PS) surface exposure, and elevated the osmotic fragility of iRBCs, but it did not affect invasion of RBCs in vitro. The modified iRBC surface triggered PS-CD36-mediated phagocytosis of iRBCs, host type I interferon (IFN-I) signaling, and T cell differentiation, leading to improved host survival. This study reveals a previously unknown role of PyEBL in regulating host-pathogen interaction and innate immune responses, which may be explored for developing disease control strategies. IMPORTANCE Malaria is a deadly parasitic disease that continues to afflict hundreds of millions of people every year. Infections with malaria parasites can be asymptomatic, with mild symptoms, or fatal, depending on a delicate balance of host immune responses. Malaria parasites enter host red blood cells (RBCs) through interactions between parasite ligands and host receptors, such as erythrocyte-binding-like (EBL) proteins and host Duffy antigen receptor for chemokines (DARC). Plasmodium yoelii EBL (PyEBL) is known to play a role in parasite invasion of RBCs. Here, we show that PyEBL also affects disease severity through modulation of host immune responses, particularly type I interferon (IFN-I) signaling. This discovery assigns a new function to PyEBL and provides a mechanism for developing disease control strategies.Yu-chih PengYanwei QiCui ZhangXiangyu YaoJian WuSittiporn PattaradilokratLu XiaKeyla C. TumasXiao HeTakahiro IshizakiChen-Feng QiAnthony A. HolderTimothy G. MyersCarole A. LongOsamu KanekoJian LiXin-zhuan SuAmerican Society for MicrobiologyarticlePlasmodiummouseerythrocyte-binding-likeEBLinterferonpathogen-host interactionMicrobiologyQR1-502ENmBio, Vol 11, Iss 1 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Plasmodium mouse erythrocyte-binding-like EBL interferon pathogen-host interaction Microbiology QR1-502
spellingShingle	Plasmodium mouse erythrocyte-binding-like EBL interferon pathogen-host interaction Microbiology QR1-502 Yu-chih Peng Yanwei Qi Cui Zhang Xiangyu Yao Jian Wu Sittiporn Pattaradilokrat Lu Xia Keyla C. Tumas Xiao He Takahiro Ishizaki Chen-Feng Qi Anthony A. Holder Timothy G. Myers Carole A. Long Osamu Kaneko Jian Li Xin-zhuan Su <named-content content-type="genus-species">Plasmodium yoelii</named-content> Erythrocyte-Binding-like Protein Modulates Host Cell Membrane Structure, Immunity, and Disease Severity
description	ABSTRACT Erythrocyte-binding-like (EBL) proteins are known to play an important role in malaria parasite invasion of red blood cells (RBCs); however, any roles of EBL proteins in regulating host immune responses remain unknown. Here, we show that Plasmodium yoelii EBL (PyEBL) can shape disease severity by modulating the surface structure of infected RBCs (iRBCs) and host immune responses. We identified an amino acid substitution (a change of C to Y at position 741 [C741Y]) in the protein trafficking domain of PyEBL between isogenic P. yoellii nigeriensis strain N67 and N67C parasites that produce different disease phenotypes in C57BL/6 mice. Exchanges of the C741Y alleles altered parasite growth and host survival accordingly. The C741Y substitution also changed protein processing and trafficking in merozoites and in the cytoplasm of iRBCs, reduced PyEBL binding to band 3, increased phosphatidylserine (PS) surface exposure, and elevated the osmotic fragility of iRBCs, but it did not affect invasion of RBCs in vitro. The modified iRBC surface triggered PS-CD36-mediated phagocytosis of iRBCs, host type I interferon (IFN-I) signaling, and T cell differentiation, leading to improved host survival. This study reveals a previously unknown role of PyEBL in regulating host-pathogen interaction and innate immune responses, which may be explored for developing disease control strategies. IMPORTANCE Malaria is a deadly parasitic disease that continues to afflict hundreds of millions of people every year. Infections with malaria parasites can be asymptomatic, with mild symptoms, or fatal, depending on a delicate balance of host immune responses. Malaria parasites enter host red blood cells (RBCs) through interactions between parasite ligands and host receptors, such as erythrocyte-binding-like (EBL) proteins and host Duffy antigen receptor for chemokines (DARC). Plasmodium yoelii EBL (PyEBL) is known to play a role in parasite invasion of RBCs. Here, we show that PyEBL also affects disease severity through modulation of host immune responses, particularly type I interferon (IFN-I) signaling. This discovery assigns a new function to PyEBL and provides a mechanism for developing disease control strategies.
format	article
author	Yu-chih Peng Yanwei Qi Cui Zhang Xiangyu Yao Jian Wu Sittiporn Pattaradilokrat Lu Xia Keyla C. Tumas Xiao He Takahiro Ishizaki Chen-Feng Qi Anthony A. Holder Timothy G. Myers Carole A. Long Osamu Kaneko Jian Li Xin-zhuan Su
author_facet	Yu-chih Peng Yanwei Qi Cui Zhang Xiangyu Yao Jian Wu Sittiporn Pattaradilokrat Lu Xia Keyla C. Tumas Xiao He Takahiro Ishizaki Chen-Feng Qi Anthony A. Holder Timothy G. Myers Carole A. Long Osamu Kaneko Jian Li Xin-zhuan Su
author_sort	Yu-chih Peng
title	<named-content content-type="genus-species">Plasmodium yoelii</named-content> Erythrocyte-Binding-like Protein Modulates Host Cell Membrane Structure, Immunity, and Disease Severity
title_short	<named-content content-type="genus-species">Plasmodium yoelii</named-content> Erythrocyte-Binding-like Protein Modulates Host Cell Membrane Structure, Immunity, and Disease Severity
title_full	<named-content content-type="genus-species">Plasmodium yoelii</named-content> Erythrocyte-Binding-like Protein Modulates Host Cell Membrane Structure, Immunity, and Disease Severity
title_fullStr	<named-content content-type="genus-species">Plasmodium yoelii</named-content> Erythrocyte-Binding-like Protein Modulates Host Cell Membrane Structure, Immunity, and Disease Severity
title_full_unstemmed	<named-content content-type="genus-species">Plasmodium yoelii</named-content> Erythrocyte-Binding-like Protein Modulates Host Cell Membrane Structure, Immunity, and Disease Severity
title_sort	<named-content content-type="genus-species">plasmodium yoelii</named-content> erythrocyte-binding-like protein modulates host cell membrane structure, immunity, and disease severity
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/5f2b539ed3854aa99666af61979e8b83
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<named-content content-type="genus-species">Plasmodium yoelii</named-content> Erythrocyte-Binding-like Protein Modulates Host Cell Membrane Structure, Immunity, and Disease Severity

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