Gay et al. identify a Toxoplasma gondii secreted effector that recruits NuRD transcriptional repressor and blocks IFN-γ–stimulated STAT1-dependent gene expression, thus dampening host responses to infection.

Amyloid fibres attract considerable interests due to their biological roles in neurodegenerative diseases and their potentials as functional biomaterials. We describe here a completely new finding about an intrinsic signal of amyloid fibres in the near infrared (NIR) range. When combined with their recently reported blue luminescence, it paves the way toward new blueprints for label-free detections of amyloid deposits within in vitro up to in vivo contexts. The blue luminescence allows for staining-free characterization of amyloid deposits within human samples. The NIR signal offers promising prospects for innovative diagnostic strategies of neurodegenerative diseases; a need to improve medical care and to develop new therapies. As a proof of concept, we demonstrate direct detection of amyloid deposits within brains of living aged "Alzheimer's" mice using non-invasive and contrast agent-free imaging. UV-Vis-NIR optical properties of amyloids opens new research avenues across amyloidoses as well as for next generation biophotonic devices.

Toxoplasma gondii is an important food and waterborne pathogen causing toxoplasmosis, a potentially severe disease in immunocompromised or congenitally infected humans. Available therapeutic agents are limited by suboptimal efficacy and frequent side effects that can lead to treatment discontinuation. Here we report that the benzoxaborole AN3661 had potent in vitro activity against T. gondii. Parasites selected to be resistant to AN3661 had mutations in TgCPSF3, which encodes a homologue of cleavage and polyadenylation specificity factor subunit 3 (CPSF‐73 or CPSF3), an endonuclease involved in mRNA processing in eukaryotes. Point mutations in TgCPSF3 introduced into wild‐type parasites using the CRISPR/Cas9 system recapitulated the resistance phenotype. Importantly, mice infected with T. gondii and treated orally with AN3661 did not develop any apparent illness, while untreated controls had lethal infections. Therefore, Tg CPSF3 is a promising novel target of T. gondii that provides an opportunity for the development of anti‐parasitic drugs.

Introductory paragraph The protozoan parasite Toxoplasma gondii has co-evolved with its homeothermic hosts, human included, strategies that drive its quasi asymptomatic persistence in hosts, hence optimizing the chance of transmission to new hosts. Persistence which starts with a small subset of parasites that escape from the host immune killing and colonize the so-called immune privileged tissues where they differentiate into a low replicating stage, is driven by the IL-12 and IFN-γ axis. The recent characterization of a Toxoplasma effector family delivered into the host cell where it rewires the host cell gene expression has allowed identifying regulators of the IL-12-IFN-γ axis including repressors. We now report on the dense granule-resident effector, called TEEGR (Toxoplasma E2F4-associated EZH2-inducing Gene Regulator) that counteracts the NF-κB signaling pathway. Once exported in the host cell TEEGR ends up in the nucleus where it not only complexes with E2F3 and E2F4 host transcription factors to induce gene expression but also promotes shaping of a nonpermissive chromatin through its capacity to switch on EZH2. Remarkably, EZH2 fosters the epigenetic silencing of a subset of NF-κB-regulated cytokines thereby strongly contributing to the host immune equilibrium that influencing the host immune response and in mice promotes parasite persistence.