Biology subjects

Sizaret, D.

Publications and source records attributed to Sizaret, D..

3 recordsLinked to original sources

bioRxiv2026

A rapid agarose-free protocol for preparing human organotypic lung cultures to study respiratory virus infection and evaluate antivirals ex vivo

We describe a standardized and reproducible procedure to generate human organotypic lung cultures from surgical lung resection for the study of respiratory infections. The protocol details tissue harvesting, biopsy punching, mechanical slicing, culture at the air-liquid interface. This technique enables robust ex vivo infections of human lung tissue with respiratory viruses, including Influenza A and Nipah. The described system can be used to study host-pathogen interactions, analyze innate immune responses, and evaluate antiviral candidates in physiologically relevant human lung tissue. For complete details on the use and execution of this protocol, please refer to Cezard et al1.

pathology↗

bioRxiv2025

Cis-aconitate therapy protects against influenza mortality by dual targeting of viral polymerase and ERK/AKT/NF-κB signaling

Influenza virus poses a significant global health challenge, causing approximately 500,000 deaths annually. Its ability to evade antiviral treatments and vaccine-induced immunity underscores the need for novel therapeutic approaches. Our study identifies cis-aconitate (cis-aco), a mitochondria-derived metabolite, as a potent dual-action agent against influenza, independently of its metabolic derivative, itaconate. Cis-aco impairs viral polymerase activity, suppressing viral mRNA expression and protein synthesis to inhibit replication across a range of influenza subtypes. This antiviral efficacy is confirmed in ex vivo human airway and lung organotypic models. Beyond its antiviral properties, cis-aco exhibits potent anti-inflammatory effects, disrupting key inflammatory cascades and reducing the secretion of inflammatory mediators. In a mouse model of influenza pneumonia, cis-aco mitigates viral replication, inflammation, and immune cell activation, significantly improving survival. Notably, its efficacy persists even when administered at later stages of infection, when oseltamivir/Tamiflu(R) is no longer effective. These findings position cis-aco as a promising influenza treatment, combining antiviral and anti-inflammatory benefits within a clinically relevant timeframe.

immunology↗

bioRxiv2024

From tissue to subcellular level : imaging human precision-cut lung slices (PCLS) to gain insight into pandemic bacterial or viral infections

We describe a method for the generation and deep imaging of human precision-cut lung slices (PCLS). PCLS bridge the gap between in vivo and in vitro studies, providing a robust system for visualizing events from tissue to subcellular levels in the three-dimensional lung environment, with the preservation of all resident cell types and cell-cell interactions. They also constitute a validated model for studying host cell-pathogen interactions. Here, we detail the generation of human PCLS, followed by their infection and imaging by laser scanning confocal microscopy and transmission electron microscopy (TEM). We establish the conditions for ex vivo infection and replication of two pathogens of relevance to human respiratory health: a virus (SARS-CoV-2) and a bacterium (Mycobacterium tuberculosis, Mtb). PCLS can be obtained in a single day, infected the next day, and were successfully cultivated for up to a week in this study. Imaging was performed on fixed samples. The preparation of PCLS took one day for confocal imaging and five days for TEM imaging. All procedures are readily adaptable to explore other pathogens and other species and are easy to implement by users with experience in tissue culture. Some specialist equipment (an Alabama tissue slicer) is required for PCLS generation.

cell biology↗