Inflammasome, bacterial infections and autoinflammation

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Research themes

General interests:

Our lab has long been interested in deciphering host-pathogens interactions taking place during bacterial infections with a focus on innate immune responses and bacterial virulence factors modulating these responses. Lately, we have been exploiting our inflammasome expertise to study autoinflammatory syndromes (inflammasomopathies) and particularly Familial Mediterranean Fever. We are now developing this translational research in collaboration with clinicians.

The 3 research axes of the lab are thus:

1-Bacterial virulence factors and their interaction with host cells

2-Innate immune mechanisms during infection with the cytosolic bacterium Francisella tularensis

3-Inflammasome and autoinflammatory syndromes


Theme 1: Bacterial virulence factors and their interaction with host cells

We are studying two bacterial pathogens: Francisella tularensis, the agent of tularemia and Staphylococcus aureus, a major human pathogen causing numerous nosocomial (hospital-acquired) and community-acquired diseases.

Francisella tularensis is an intracellular bacterium replicating within the cytosol of macrophages. The key feature in Francisella virulence lies in its ability to lyse the phagosomal membrane to escape into the host cytosol. This step is dependent on an atypical Type VI secretion system (T6SS). We are interested in identifying the T6SS effectors responsible for Francisella virulence and how they function at the molecular level in interactions with host proteins.

Francisella T6SS: Molecular Modeling of IglG protein, the Francisella PAAR-like protein, docked on a VgrG trimer (Green)-in collaboration with L. Terradot (MMSB; Lyon). Adapted from Rigard R., Bröms J. et al. Plos Pathogens 2016

Staphylococcus aureus is a fascinating bacterium that can switch from one of the most successful human commensal to one of the most successful human pathogen. Its pathogenicity is associated with an arsenal of secreted virulence factors including some very potent pore-forming toxins. We are studying S. aureus pore forming toxins particularly in regards to their host receptors and the immune response they are triggering. These studies led us to develop a novel animal model (humanized C5aR1 knock-in mice) to understand the role of toxins in vivo.

S. aureus pore-forming toxins can lyse not only inflammatory monocytes but also red blood cells in a receptor-dependent manner (hemolysis assay with 4 different toxins at various dilutions)-Adapted from Spaan AN, Reyes-Robles T. et al. Cell Host Microbes 2015.


Theme 2: Innate immune mechanisms during infection with the cytosolic bacterium Francisella tularensis

F. tularensis and the closely related strain F. novicida are used in the lab as a tool to study the cytosolic immune responses of macrophages. The basics questions we are addressing are the following: 1-How does a host cell detect invasion in its cytosol? 2- How does a host cell react to kill cytosolic bacteria? 3- How does eicosanoids regulate immune responses to Francisella infection ?

Particularly, F. tularensis triggers activation of a type I IFN response and of the AIM2 inflammasome pathway upon infection of the macrophage cytosol. The AIM2 inflammasome is a molecular platform sensing the presence of double-stranded DNA in the cytosol and leading to activation of caspase-1. Caspase-1 is an inflammatory caspase triggering the maturation and the secretion of the pro-inflammatory cytokines IL-1β and IL-18 and the death of the infected cell in a process termed pyroptosis. Recently we have identified the Interferon-induced GBPs as antibacterial immune effectors lysing Francisella in the host cytosol and leading to inflammasome activation.

Gbp5 (red) is targeted to Francisella (Green), inhibits bacterial growth and promotes bacterial replication. Confocal images of an infected macrophage (left panel) and single cell quantification of intracellular bacterial load by ImageStreamX-Adapted from Meunier E, Wallet P. et al. Nature Immunol. 2015


In the past few years, functional links have been uncovered between inflammasome and eicosanoids, thanks to recent advances in lipidomics. Eicosanoids are lipid mediators of inflammation. Even if their role has long been described in the innate immune response, little is known about their roles in intracellular bacterial infectious models.  That is why we decided to study the relations between eicosanoids and the immune responses to Francisella infection in mice by characterizing the involvement of eicosanoids in AIM2 inflammasome regulation, and vice versa. A better understanding of this system may allow the development of new drugs helping the host in its fight against the infection.


Theme 3: Inflammasome and autoinflammatory syndromes

Mutations in inflammasome sensors-encoding genes can trigger autoinflammatory diseases termed inflammasomopathies. This theme is developed along two axes, the first one tackles the dysregulation of inflammasome in a monogenic autoinflammatory disease termed Familial Mediterranean Fever, the second one studies the dysregulation of the inflammasome in complex autoinflammatory diseases associated with recurrent fever (e.g. Still’s disease).

FMF is associated with mutation in the inflammasome sensor Pyrin. In tight interactions with the Lyon Hospitals, we are studying inflammasome function in cells from FMF patients and healthy donors. We have also developed several cell lines models to study the impact of FMF-associated Pyrin mutations on the inflammasome. Our goal is to better understand the pathway leading to Pyrin inflammasome activation in healthy individuals and in FMF patients to promote a better understanding of the pathophysiological mechanisms of the disease. Furthermore, our secondary goal is promote is a better diagnosis of FMF.

Real time cell death assay demonstrating that monocytes from FMF patients are hyper-responsive to the bacterial toxin TcdB. Adapted from Jamilloux Y, Lefeuvre L, Magnotti F et al. Rheumatology 2017



INSERM,  University of Lyon, ANR, FINOVI (, DGA

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This project has received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement no ERC-2012-StG_20111109.
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