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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

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 languageEnglish
Article number4851
JournalNature Communications
Volume12
Issue number1
DOIs
StatePublished - 1 Dec 2021

Funding

FundersFunder number
Benoziyo Endowment Fund for the Advancement of Science
Jeanne and Joseph Nissim Foundation for Life Sciences Research
Weizmann - Sao Paulo Research Foundation
Horizon 2020 Framework Programme
H2020 European Research Council757743
Seventh Framework Programme337581
European Research Council
Fundação de Amparo à Pesquisa do Estado de São Paulo
Israel Science Foundation2235/16, 619/16, 1637/20
Instituto Serrapilheira

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