Université de Strasbourg

USIAS Fellows seminar

October 8, 2019
From 15:30 until 17:00
Salle Asie, Misha

By Roméo Ricci (Fellow 2017)

How inter-organelle communication in the cell links danger signals to inflammation

Inflammation is necessary to alleviate tissue damage caused by pathogens, toxic agents or injury. Uncontrolled inflammation, however, can cause disease as exemplified in auto-immune diseases, chronic infections or allergic reactions. Importantly, chronic inflammation also constitutes an important hallmark that contributes to development of cancer, type 2 diabetes as well as neurodegenerative disorders.

The first line of defense induced by toxic/infectious agents or tissue injury is the so called innate immune response. Apart from immune cells, any cell in our body that is frequently exposed to environmental stresses are equipped with a whole arsenal of danger sensing molecules (pattern-recognition receptors). These receptors allow for immediate recognition of a whole variety of dangerous signals.

Our laboratory focuses on the inflammasome, one of the most versatile and powerful intracellular stress sensing system evolved in evolution. The inflammasome comprises a molecular platform in which specialized receptors that can recognize a specific danger signal are assembled together with an enzymatic machinery that produces the pro-inflammatory cytokines interleukin 1beta and interleukin 18. Eventually, inflammasome activation will culminate in an inflammatory cell death described as pyroptosis. These reactions are the basis for subsequent inflammatory responses that include recruitment of immune cells and production of other pro-inflammatory factors.

Using state-of-the-art imaging approaches in our laboratory, we show how inflammasome assembly in macrophages occurs in time and space providing evidence for dynamic remodeling of endoplasmic reticulum and Golgi membrane contact sites to be at the basis of this fundamental innate immune response.

Illustration: Interplay of Golgi and ER membranes. Green: Inflammasome Receptor on Golgi membranes, Red: ER membranes

Investissements d'Avenir