| dc.identifier.citation | 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, Regev-Rudzki N., Malaria parasites both repress host CXCL10 and use it as a cue for growth acceleration, Nature communications, 2021, 12, 1, 4851 | en |
| dc.description.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 inhi-
bition 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. | en |
