L’immunité innée au niveau des muqueuses

Members

Achille BROGGI

Research Officer

About

Team leader: Dr Achille Broggi
The intestine: a key organ for our health

The intestine isn't just a digestive organ: it's also a key player in our defense against microbes. It's lined with an epithelium—a thin layer of cells—that acts as a protective barrier. This epithelium is constantly exposed to billions of microbes: some are beneficial (the microbiota), others can be dangerous (pathogens). To stay healthy, the intestine must maintain a delicate balance between defense, repair And tolerance.

When this balance is disrupted, the barrier becomes fragile, which promotes infections and can lead to chronic diseases such as IBD (chronic inflammatory bowel diseases, e.g. Crohn's disease).

Our team seeks to understand how immune cells, epithelial cells and intestinal microbes communicate with each other to maintain this balance.

Axis 1: Type III interferons – Protection that can sometimes become harmful

Responsible: Dr Achille Broggi

Type III interferons (IFN-λ) are molecules produced during infections, especially viral ones. They help defend the intestine by protecting cells and limiting inflammation.

But if these molecules are produced for too long or at the wrong time (for example in response to an unbalanced microbiota), they can block repair processes and maintain inflammation.
We are studying how these interferons work, to better understand when and how they help or harm to gut health, and how we might regulate to avoid negative effects.

**Small intestinal organoids cultured at the air-liquid interface (ALI) to simulate a normal intestine.** In red: Ki67 marks proliferating cells; in green: DAPI stains cell nuclei. *Image credit: Julien Mambu (CIML).*

Axis 2: Malnutrition and intestinal immunity

Responsible: Dr Julie Tomas, Dr. Achille Broggi

Malnutrition, especially in children, makes the gut more fragile. It weakens the immune system, alters the microbiota, and reduces the effectiveness of vaccines.
We seek to understand How malnutrition disrupts intestinal defenses, and how we could restore them.
We are testing solutions such as using probiotics or of beneficial molecules to strengthen immunity and improve the effectiveness of nutritional treatments, particularly in vulnerable children.

**Schematic representation of the consequences of malnutrition in the intestine.** *Image credit: Julie Tomas (CIML).*

Axis 3: Vitamin B5 and intestinal repair

Responsible: Prof. Franck Galland, Dr.Achille Broggi

To repair themselves, the cells of the intestine need energy. This energy is produced by structures called mitochondria, a bit like the “power plants” of cells.

We discovered that an enzyme called Vnn1, produced in the epithelium, helps transform nutrients into vitamin B5, a key element for the proper functioning of mitochondria.
By boosting this metabolic pathway, Vnn1 improves the ability of the intestinal barrier to repair itself.
Our work aims to better understand this interaction between metabolism, microbiota and repair, to propose new therapeutic approaches.

**Schematic representation of VNN1 enzyme activity in the intestine.** VNN1 converts the Coenzyme A (CoA) metabolite, pantetheine, into its bioactive metabolites: pantothenate (vitamin B5) and cysteamine. Vitamin B5 enters cells and replenishes CoA stores, while cysteamine balances cellular redox status. This process improves mitochondrial function, supports epithelial cell vitality, and creates a favorable anaerobic environment for beneficial bacteria in the intestinal lumen. *Image credit: Franck Galland (CIML).*

These three axes — antiviral immunity, nutrition And cellular metabolism — are complementary. Together, they allow us to better understand how to maintain a healthy intestine, capable of defending and repairing itself effectively.

Our research has concrete applications for the treatment of infections, of the inflammatory diseases of the intestine and the long-term effects of malnutrition, especially in children.