Malaria parasites both repress host CXCL10 and use it as a cue for growth acceleration

Yifat Ofir-Birin; Hila Ben Ami Pilo; Abel Cruz Camacho; Ariel Rudik; Anna Rivkin; Or-Yam Revach; Netta Nir; Tal Block Tamin; Paula Abou Karam; Edo Kiper; Yoav Peleg; Reinat Nevo; Aryeh Solomon; Tal Havkin-Solomon; Alicia Rojas; Ron Rotkopf; Ziv Porat; Dror Avni; Eli Schwartz; Thomas Zillinger; Gunther Hartmann; Antonella Di Pizio; Neils Ben Quashie; Rivka Dikstein; Motti Gerlic; Ana Claudia Torrecilhas; Carmit Levy; Esther N M Nolte-'t Hoen; Andrew G Bowie; Neta Regev-Rudzki

doi:10.1038/s41467-021-24997-7

Malaria parasites both repress host CXCL10 and use it as a cue for growth acceleration

Yifat Ofir-Birin, Hila Ben Ami Pilo, Abel Cruz Camacho, Ariel Rudik, Anna Rivkin, Or-Yam Revach, Netta Nir, Tal Block Tamin, Paula Abou Karam, Edo Kiper, Yoav Peleg, Reinat Nevo, Aryeh Solomon, Tal Havkin-Solomon, Alicia Rojas, Ron Rotkopf, Ziv Porat, Dror Avni, Eli Schwartz, Thomas ZillingerGunther Hartmann, Antonella Di Pizio, Neils Ben Quashie, Rivka Dikstein, Motti Gerlic, Ana Claudia Torrecilhas, Carmit Levy, Esther N M Nolte-'t Hoen, Andrew G Bowie, Neta Regev-Rudzki

Cell Biology

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Pathogens are thought to use host molecular cues to control when to initiate life-cycle transitions, but these signals are mostly unknown, particularly for the parasitic disease malaria caused by Plasmodium falciparum. The chemokine CXCL10 is present at high levels in fatal cases of cerebral malaria patients, but is reduced in patients who survive and do not have complications. Here we show a Pf 'decision-sensing-system' controlled by CXCL10 concentration. High CXCL10 expression prompts P. falciparum to initiate a survival strategy via growth acceleration. Remarkably, P. falciparum inhibits CXCL10 synthesis in monocytes by disrupting the association of host ribosomes with CXCL10 transcripts. The underlying inhibition cascade involves RNA cargo delivery into monocytes that triggers RIG-I, which leads to HUR1 binding to an AU-rich domain of the CXCL10 3'UTR. These data indicate that when the parasite can no longer keep CXCL10 at low levels, it can exploit the chemokine as a cue to shift tactics and escape.

Original language	English
Article number	4851
Pages (from-to)	1-15
Journal	Nature Communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-021-24997-7
Publication status	Published - 11 Aug 2021

Bibliographical note

Keywords

3' Untranslated Regions
Chemokine CXCL10/genetics
DEAD Box Protein 58/metabolism
ELAV-Like Protein 1/metabolism
Extracellular Vesicles/metabolism
Host-Parasite Interactions
Humans
Life Cycle Stages
Malaria, Falciparum/immunology
Monocytes/metabolism
Plasmodium falciparum/growth & development
Protein Biosynthesis
RNA, Protozoan/metabolism
Receptors, Immunologic/metabolism
Ribosomes/metabolism
THP-1 Cells

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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s41467-021-24997-7Final published version, 1.31 MBLicence: CC BY

Cite this

Ofir-Birin, Y., Ben Ami Pilo, H., Cruz Camacho, A., Rudik, A., Rivkin, A., Revach, O.-Y., Nir, N., Block Tamin, T., Abou Karam, P., Kiper, E., Peleg, Y., Nevo, R., Solomon, A., Havkin-Solomon, T., Rojas, A., Rotkopf, R., Porat, Z., Avni, D., Schwartz, E., ... Regev-Rudzki, N. (2021). Malaria parasites both repress host CXCL10 and use it as a cue for growth acceleration. Nature Communications, 12(1), 1-15. Article 4851. https://doi.org/10.1038/s41467-021-24997-7

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title = "Malaria parasites both repress host CXCL10 and use it as a cue for growth acceleration",

abstract = "Pathogens are thought to use host molecular cues to control when to initiate life-cycle transitions, but these signals are mostly unknown, particularly for the parasitic disease malaria caused by Plasmodium falciparum. The chemokine CXCL10 is present at high levels in fatal cases of cerebral malaria patients, but is reduced in patients who survive and do not have complications. Here we show a Pf 'decision-sensing-system' controlled by CXCL10 concentration. High CXCL10 expression prompts P. falciparum to initiate a survival strategy via growth acceleration. Remarkably, P. falciparum inhibits CXCL10 synthesis in monocytes by disrupting the association of host ribosomes with CXCL10 transcripts. The underlying inhibition cascade involves RNA cargo delivery into monocytes that triggers RIG-I, which leads to HUR1 binding to an AU-rich domain of the CXCL10 3'UTR. These data indicate that when the parasite can no longer keep CXCL10 at low levels, it can exploit the chemokine as a cue to shift tactics and escape.",

keywords = "3' Untranslated Regions, Chemokine CXCL10/genetics, DEAD Box Protein 58/metabolism, ELAV-Like Protein 1/metabolism, Extracellular Vesicles/metabolism, Host-Parasite Interactions, Humans, Life Cycle Stages, Malaria, Falciparum/immunology, Monocytes/metabolism, Plasmodium falciparum/growth & development, Protein Biosynthesis, RNA, Protozoan/metabolism, Receptors, Immunologic/metabolism, Ribosomes/metabolism, THP-1 Cells",

author = "Yifat Ofir-Birin and {Ben Ami Pilo}, Hila and {Cruz Camacho}, Abel and Ariel Rudik and Anna Rivkin and Or-Yam Revach and Netta Nir and {Block Tamin}, Tal and {Abou Karam}, Paula and Edo Kiper and Yoav Peleg and Reinat Nevo and Aryeh Solomon and Tal Havkin-Solomon and Alicia Rojas and Ron Rotkopf and Ziv Porat and Dror Avni and Eli Schwartz and Thomas Zillinger and Gunther Hartmann and {Di Pizio}, Antonella and Quashie, {Neils Ben} and Rivka Dikstein and Motti Gerlic and Torrecilhas, {Ana Claudia} and Carmit Levy and {Nolte-'t Hoen}, {Esther N M} and Bowie, {Andrew G} and Neta Regev-Rudzki",

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year = "2021",

month = aug,

day = "11",

doi = "10.1038/s41467-021-24997-7",

language = "English",

volume = "12",

pages = "1--15",

journal = "Nature Communications",

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Ofir-Birin, Y, Ben Ami Pilo, H, Cruz Camacho, A, Rudik, A, Rivkin, A, Revach, O-Y, Nir, N, Block Tamin, T, Abou Karam, P, Kiper, E, Peleg, Y, Nevo, R, Solomon, A, Havkin-Solomon, T, Rojas, A, Rotkopf, R, Porat, Z, Avni, D, Schwartz, E, Zillinger, T, Hartmann, G, Di Pizio, A, Quashie, NB, Dikstein, R, Gerlic, M, Torrecilhas, AC, Levy, C, Nolte-'t Hoen, ENM, Bowie, AG & Regev-Rudzki, N 2021, 'Malaria parasites both repress host CXCL10 and use it as a cue for growth acceleration', Nature Communications, vol. 12, no. 1, 4851, pp. 1-15. https://doi.org/10.1038/s41467-021-24997-7

TY - JOUR

T1 - Malaria parasites both repress host CXCL10 and use it as a cue for growth acceleration

AU - Ofir-Birin, Yifat

AU - Ben Ami Pilo, Hila

AU - Cruz Camacho, Abel

AU - Rudik, Ariel

AU - Rivkin, Anna

AU - Revach, Or-Yam

AU - Nir, Netta

AU - Block Tamin, Tal

AU - Abou Karam, Paula

AU - Kiper, Edo

AU - Peleg, Yoav

AU - Nevo, Reinat

AU - Solomon, Aryeh

AU - Havkin-Solomon, Tal

AU - Rojas, Alicia

AU - Rotkopf, Ron

AU - Porat, Ziv

AU - Avni, Dror

AU - Schwartz, Eli

AU - Zillinger, Thomas

AU - Hartmann, Gunther

AU - Di Pizio, Antonella

AU - Quashie, Neils Ben

AU - Dikstein, Rivka

AU - Gerlic, Motti

AU - Torrecilhas, Ana Claudia

AU - Levy, Carmit

AU - Nolte-'t Hoen, Esther N M

AU - Bowie, Andrew G

AU - Regev-Rudzki, Neta

PY - 2021/8/11

Y1 - 2021/8/11

N2 - Pathogens are thought to use host molecular cues to control when to initiate life-cycle transitions, but these signals are mostly unknown, particularly for the parasitic disease malaria caused by Plasmodium falciparum. The chemokine CXCL10 is present at high levels in fatal cases of cerebral malaria patients, but is reduced in patients who survive and do not have complications. Here we show a Pf 'decision-sensing-system' controlled by CXCL10 concentration. High CXCL10 expression prompts P. falciparum to initiate a survival strategy via growth acceleration. Remarkably, P. falciparum inhibits CXCL10 synthesis in monocytes by disrupting the association of host ribosomes with CXCL10 transcripts. The underlying inhibition cascade involves RNA cargo delivery into monocytes that triggers RIG-I, which leads to HUR1 binding to an AU-rich domain of the CXCL10 3'UTR. These data indicate that when the parasite can no longer keep CXCL10 at low levels, it can exploit the chemokine as a cue to shift tactics and escape.

AB - Pathogens are thought to use host molecular cues to control when to initiate life-cycle transitions, but these signals are mostly unknown, particularly for the parasitic disease malaria caused by Plasmodium falciparum. The chemokine CXCL10 is present at high levels in fatal cases of cerebral malaria patients, but is reduced in patients who survive and do not have complications. Here we show a Pf 'decision-sensing-system' controlled by CXCL10 concentration. High CXCL10 expression prompts P. falciparum to initiate a survival strategy via growth acceleration. Remarkably, P. falciparum inhibits CXCL10 synthesis in monocytes by disrupting the association of host ribosomes with CXCL10 transcripts. The underlying inhibition cascade involves RNA cargo delivery into monocytes that triggers RIG-I, which leads to HUR1 binding to an AU-rich domain of the CXCL10 3'UTR. These data indicate that when the parasite can no longer keep CXCL10 at low levels, it can exploit the chemokine as a cue to shift tactics and escape.

KW - 3' Untranslated Regions

KW - Chemokine CXCL10/genetics

KW - DEAD Box Protein 58/metabolism

KW - ELAV-Like Protein 1/metabolism

KW - Extracellular Vesicles/metabolism

KW - Host-Parasite Interactions

KW - Humans

KW - Life Cycle Stages

KW - Malaria, Falciparum/immunology

KW - Monocytes/metabolism

KW - Plasmodium falciparum/growth & development

KW - Protein Biosynthesis

KW - RNA, Protozoan/metabolism

KW - Receptors, Immunologic/metabolism

KW - Ribosomes/metabolism

KW - THP-1 Cells

U2 - 10.1038/s41467-021-24997-7

DO - 10.1038/s41467-021-24997-7

M3 - Article

C2 - 34381047

SN - 2041-1723

VL - 12

SP - 1

EP - 15

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 4851

ER -

Malaria parasites both repress host CXCL10 and use it as a cue for growth acceleration

Abstract

Bibliographical note

Keywords

UN SDGs

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