Biology subjects

Arbibe, L.

Publications and source records attributed to Arbibe, L..

2 recordsLinked to original sources

bioRxiv2020

HP1γ sets the biological age of the intestinal epithelium

Defects in RNA splicing have been linked to numerous human disorders, but remain poorly explored in inflammatory bowel disease (IBD). Here, we report that, in the gut epithelium of patients with ulcerative colitis (UC), the expression of the chromatin and alternative splicing regulator HP1{gamma} is strongly reduced. Accordingly, inactivation of the HP1{gamma} gene in the mouse gut triggered several IBD-like traits, including inflammation and dysbiosis. In parallel, we discovered that its loss of function broadly increased splicing noise, reducing requirement for canonical splicing consensus sequences, and favoring the usage of cryptic splice sites at numerous genes with key functions in gut biology. This notably resulted in the production of progerin, a noncanonical toxic splice variant of prelamin A mRNA, responsible for the Hutchinson Gilford Progeria Syndrome (HGPS) of premature aging. Likewise, production of progerin transcript was found to be a signature of colonic cells from UC patients. Thus, our study identifies HP1{gamma} as a regulator of RNA metabolism in vivo, providing a unique mechanism linking anti-inflammation and accuracy of RNA splicing in the gut epithelium. HP1 defect may confer a general disturbance in RNA splicing precision to scrutinize in IBD and more generally in accelerating aging diseases.

cell biology↗

bioRxiv2020

ROS-dependent innate immune mechanisms control Staphylococcus aureus MRSA virulence in the Drosophila larval model

Antibiotics multi-resistant Staphylococcus aureus strains constitute a major public health concern worldwide and are responsible of both healthcare- and community-associated infections. Here we have established a robust and simple S. aureus oral infection model, using Drosophila melanogaster larva, which allowed to follow S. aureus fate at the whole organism level as well as the host immune responses. Fluorescence microscopy and Light sheet 3D imaging revealed bacterial clustering at the posterior midgut that displays neutral pH. Our study demonstrates that S. aureus infection triggers host H2O2 production through Duox enzyme, consequently empowering antimicrobial peptides production through Toll pathway activation. We also show that catalase-mediated quenching of H2O2 not only enhances S. aureus survival but also minimizes host antimicrobial response, hence reducing bacterial clearance in vivo. Finally, we confirm the versatility of this model by demonstrating the colonization and host stimulation capacities of two other bacterial pathogens: Salmonella Typhimurium and Shigella flexneri. Overall, the drosophila larva may constitute a general model to follow in vivo host innate immune responses triggered upon infection with human pathogens.

microbiology↗