Cell signalling in bacterial infections
In response to the emergence of antibiotic resistance mechanisms in many pathogenic bacteria, it is necessary to develop innovative therapeutic strategies based on the characterization of new molecular determinants of virulence and cellular factors involved in critical host-pathogen interactions.
In this regard, the molecular mechanisms responsible for the activation and regulation of innate immunity, which constitutes the first line of defense against pathogens, are of particular interest. During an infection, bacteria are detected by pathogen recognition receptors (PRRs) of immune cells, but also epithelial and endothelial cells that act as immune sentinels. After recognition of bacterial molecular patterns, PRRs trigger pro-inflammatory signaling pathways that lead to the secretion of a wide range of immune effectors such as cytokines, chemokines and antimicrobial peptides.
Our laboratory works at the interface between immunology and cell biology and studies the molecular mechanisms involved in the detection of infectious bacteria and the control of innate immunity. We combine interfering RNA screens, live cell fluorescence microscopy, electron microscopy, proteomics and transcriptomics to characterize at the molecular level new host-pathogen interactions that can be targeted by anti-infective treatments. The Gram-negative bacterium Shigella flexneri is our main model of infection.
Top 5 publications
1- García-Weber D, Arrieumerlou C. ADP-heptose: a bacterial PAMP detected by the host sensor ALPK1. Cell Mol Life Sci. 2021 Jan;78(1):17-29.
2- Carson D, Barry R, Hopkins EGD, Roumeliotis TI, García-Weber D, Mullineaux-Sanders C, Elinav E, Arrieumerlou C, Choudhary JS, Frankel G. Citrobacter rodentium induces rapid and unique metabolic and inflammatory responses in mice suffering from severe disease. Cell Microbiol. 2020 Jan;22(1):e13126.
3- García-Weber D, Dangeard AS, Cornil J, Thai L, Rytter H, Zamyatina A, Mulard LA, Arrieumerlou C. ADP-heptose is a newly identified pathogen-associated molecular pattern of Shigella flexneri. EMBO Rep. 2018 Dec;19(12).
4- Milivojevic M, Dangeard AS, Kasper CA, Tschon T, Emmenlauer M, Pique C, Schnupf P, Guignot J, Arrieumerlou C. ALPK1 controls TIFA/TRAF6-dependent innate immunity against heptose-1,7-bisphosphate of gram-negative bacteria. PLoS Pathog (2017) Feb 21;13(2):e1006224.
5- Gaudet RG, Guo CX, Molinaro R, Kottwitz H, Rohde JR, Dangeard AS, Arrieumerlou C, Girardin SE, Gray-Owen SD. Innate Recognition of Intracellular Bacterial Growth Is Driven by the TIFA-Dependent Cytosolic Surveillance Pathway. Cell Rep (2017), May 16;19(7):1418-1430.
Dernières publications sur HAL :
- [hal-02635923] Simultaneous analysis of large-scale RNAi screens for pathogen entryby email@example.com (Pauli Raemoe) on 27 May 2020 at 19h19
Background: Large-scale RNAi screening has become an important technology for identifying genes involved in biological processes of interest. […]