Mechanobiology of Host-Microbe Interactions

The Mechano-biology of Host–Microbe Interactions team aims to understand how tissue microarchitecture, mechanical forces, and the local microenvironment shape pathogen interactions at mucosal barrier interfaces. Our research primarily focuses on intestinal infections, using Shigella as a model pathogen. These bacteria invade epithelial cells and hijack the host intracellular machinery to propel themselves and spread rapidly to neighboring cells. This process triggers severe inflammation of the colon, leading to acute diarrhea that can be life-threatening, particularly in children under five years of age.

Like Shigella, many human pathogens are strictly human-restricted, making the study of pathophysiology at the tissue and organ levels in human-relevant contexts a major challenge. Over the past years, the team has developed a recognized expertise in the development and use of organ-on-chip (OoC) technologies for infection biology, demonstrating the high relevance of these alternative in vitro models in the field of infectiology. In particular, we have shown that Shigella infectivity is highly sensitive to mechanical forces associated with intestinal peristalsis. Building on this discovery, our goal is now to identify the strategies employed by Shigella to manipulate mechano-sensitive host pathways that promote bacterial dissemination across the epithelium.

A major axis of the lab is dedicated to continuously advancing the human relevance of in vitro models based on organs-on-chip and micro-physiological systems, combining microfabrication and microfluidics solution that can be used easily by biologists. We design complex intestinal OoC platforms that integrate key components of gut physiology, including immune cells, the enteric nervous system, inflammatory processes, and the intestinal microbiota. These systems allow us to recapitulate the dynamic, multicellular nature of the intestinal barrier under controlled mechanical and biochemical conditions.

Our research is inherently interdisciplinary, spanning cell biology, genetics, microbiology, mechanobiology, and bioengineering. In parallel, the lab is involved in numerous collaborative projects focused on the development of novel OoC models of the respiratory tract, with the aim of improving the understanding of respiratory infections and accelerating the evaluation of therapeutic strategies.

Ongoing

• France 2030-Université de Lille- Cross-Disciplinary Project: CDP MOSAIC

The interdisciplinary MOSAIC project addresses the urgent need to develop new methodological approaches (NAMs) that do not rely on animal models and better reproduce human physiology in vitro to advance translational research. MOSAIC aims to develop miniaturized devices known as organ-on-chip systems to improve our understanding of infectious and chronic diseases. This excellence-driven project brings together a consortium of 4 research units, 8 research teams, 2 hospitals, and the Lille Natural History Museum.

https://initiative-excellence.univ-lille.fr/nos-projets-structurants/mener-une-recherche-dexcellence/cross-disciplinary-projects/cdp-mosaic

• France 2030 PEPR MED-OOC : projet HITOC

The HITOC project combines stem cell biology, neuroscience, infection biology, microfluidics, and microelectronics to develop a new generation of multi-segment, neuro-competent intestine-on-chip models. The goal is to better understand host–pathogen interactions and microbial signaling during viral and bacterial infections, with a particular focus on the gut–brain axis.
This project is conducted in collaboration with four additional laboratories from Inserm, CNRS, Aix-Marseille University, and Institut Pasteur.

https://www.pepr-medooc.fr/projet/developpement-dun-modele-ooc-intestinal-multi-segmentaire-et-neurocompetent-a-partir-de-cellules-souches-hipsc-pour-letude-des-maladies-infectieuses-intestinales-hitoc/

• France 2030 PEPR TRANSCEND-ID

The main objective of this project is to establish an immunocompetent, patient-derived autologous intestine-on-chip model that reproduces the structural and functional complexity of the human intestinal mucosa and its interactions with the immune system and environment. This will enable a better understanding of chronic inflammatory bowel diseases(IBD).
This project is carried out in collaboration with two other Inserm laboratories: the INFINITE unit (Lille) and Institut Imagine (Paris).

• ANRS MIE : Projet Loc Mtb

This collaborative project with the International Center for Research in Infectiology (CIRI, Lyon) aims to better understand the earliest stages of pulmonary infection by Mycobacterium tuberculosis, the causative agent of tuberculosis. It relies on a lung-on-chip model developed in the laboratory that faithfully reproduces human alveolar physiology. This innovative approach will allow highly sensitive analysis of the infection capacity of clinical isolates and characterization of their early pathophysiological effects on human-mimetic alveolar tissue.

• Partenariat Hubert Curien Franco-Bulgare – Programme RILA

This international pilot project, conducted in collaboration with the Stephan Angeloff Institute of Microbiology (Sofia, Bulgaria), aims to better understand the early mechanisms of pulmonary inflammation leading to fibrotic interstitial lung diseases. In particular, it investigates the role of internal RNA modifications, especially m6A methylation, in amplifying pro-inflammatory immune responses, using advanced alveolar lung-on-chip models.