Fabrice LAURENT

Information

Scientific interests and projects

General scientific interests: Apicomplexa and Mucosal Immunity (AIM) team is working on two apicomplexan parasites with intestinal tropism, Cryptosporidium and Eimeria. Historically our research on cryptosporidiosis mainly concerned investigations on the protective and pathological immune responses. However, we extend our researches and recently start to characterize the molecular mechanisms that govern Cryptosporidium/intestinal epithelial cell interactions and the long term consequences of the infection on intestinal homeostasis and immune disorders. In man and farm animals, cryptosporidiosis is poorly controlled and we wish to combine two complementary strategies for an efficient control of the disease. Based on strong dependence of functional immune responses for controlling Cryptosporidium we wish to develop immunostimulatory strategies dedicated to neonates in order to strengthen their ability to limit parasite growth. Drug therapies are limited both in human and livestock, we therefore aim to develop new potent molecules to control parasite development.

Scientific activities to be developed in the framework of Parafrap:
I-Virulence factors: Thanks to transgenesis now available in the laboratory we wish to identify cryptosporidium virulence factors that co-opt specific host-epithelial cell signaling pathways upon invasion and development.

II- Gut physiopathology: Infection of young individuals by C. parvum induces a long-term defect on intestinal gut physiology and this has been linked to the occurrence of Irritable Bowel Syndrome (IBS). We plan to investigate the contribution of Paneth cells (PC) and their antimicrobial peptides on the onset of this intestinal disorder.

III- Control strategies: In collaboration with several international teams including Ali Hakimi’s team from Parafrap with whom we recently identified a first promising target (CPSF3) we wish to further develop our therapeutic arsenal against Cryptosporidium, from drug screening to molecular target identification and in vivo final validation (rodent and large animal models).

Top 5 publications of the last 5 years

1. C. Swale, A. Bougdour, A. Gnahoui-David, J. Tottey, S. Georgeault, F. Laurent, A. Palencia and Mohamed-Ali Hakimi, Metal-captured inhibition of pre-mRNA processing activity by CPSF3 controls Cryptosporidium infection Science Translational Medicine, 11(517): eaax7161. doi: 10.1126/scitranslmed.aax7161

2. Potiron L, Lacroix-Lamandé S, Marquis M, Levern Y, Fort G, Franceschini I, Laurent F. Batf3-Dependent Intestinal Dendritic Cells Play a Critical Role in the Control of Cryptosporidium parvum Infection. J Infect Dis. 2019 Feb 23;219(6):925-935. doi: 10.1093/infdis/jiy528

3. Diallo MA, Sausset A, Gnahoui-David A, Silva ARE, Brionne A, Le Vern Y, Bussière FI, Tottey J, Lacroix-Lamandé S, Laurent F, Silvestre A. Eimeria tenella ROP kinase EtROP1 induces G0/G1 cell cycle arrest and inhibits host cell apoptosis. Cellular Microbiology. 2019 Jul;21(7):e13027. doi: 10.1111/cmi.13027.

4. Riba A, Olier M, Lacroix-Lamandé S, Lencina C, Bacquié V, Harkat C, Gillet M, Baron M, Sommer C, Mallet V, Salvador-Cartier C, Laurent F, Théodorou V, Ménard S. Microbiota dysbiosis induced by defect of Paneth cells triggers visceral hypersensitivity in mice. Gastroenterology. 2017 Dec;153(6):1594-1606.e2. doi: 10.1111/cmi.12632.

5. de Sablet T, Potiron L, Marquis M, Bussière FI, Lacroix-Lamandé S, Laurent F. Cryptosporidium parvum increases intestinal permeability through interaction with epithelial cells and IL-1β and TNFα released by inflammatory monocytes. Cell Microbiol. 2016 Dec;18(12):1871-1880. 10.1111/cmi.12632.