1. Malaria parasites both repress host CXCL10 and use it as a cue for growth acceleration.
- Author
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Ofir-Birin Y, Ben Ami Pilo H, Cruz Camacho A, Rudik A, Rivkin A, Revach OY, 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, and Regev-Rudzki N
- Subjects
- 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, Plasmodium falciparum metabolism, Protein Biosynthesis, RNA, Protozoan metabolism, Receptors, Immunologic metabolism, Ribosomes metabolism, THP-1 Cells, Chemokine CXCL10 metabolism, Malaria, Falciparum parasitology, Plasmodium falciparum physiology
- 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., (© 2021. The Author(s).)
- Published
- 2021
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