Marie-France
CESBRON-DELAUW

Information

Scientific interests and projects

The BNI team is interested in the innate control of Toxoplasma gondii infectivity.

Infectivity refers to the capacity of a parasite to infect an individual. It involves pathogenrecognition systems, and the diversification of responses relies on the combined genetic diversity of both host and pathogen. We have established that in the rat model the control of Toxoplasma infectivity is genetically controlled by Toxo1, a single locus located on the rat chromosome 10. In resistant rats, the parasite elimination occurs at the site of infection (intestinal barrier) and involves the rapid killing of infected resident macrophages which in turn contributes to the lack of parasite dissemination. In vitro, infected resistant rat macrophages trigger the NOD-like receptor NLRP1a/Caspase-1 pathway to induce the death of both parasites and their hosting macrophages. This is parasite-induced and differs among T. gondii genotypes. Thus, having demonstrated that the parasite fate depends on both the Toxo1 locus genotype (LEW or BN origin) and the parasite genotype, we are interested in the characterization of factor(s) and pathway(s) which activate the Toxo1- dependent resistance to toxoplasmosis.

Our ongoing strategy is based on global comparative analyses of -i) resistant vs susceptible macrophages functions before and following parasite infection and -ii) a set of parasite mutant vs wildtype capable to bypass the resistance. Bioinformatics analysis will combine results from comparative proteomics, transcriptomics and metabolics. Candidate signaling/metabolic host pathway(s) and gene(s) will be validated using classical reverse genetics, biochemical and cellular studies

Top 5 publications of the last 5 years

1. Cavailles P, Flori P, Papapietro O, Bisanz C, Massera C, Cristinelli S, Jublot D, Bastien O, Loeuillet C, Aldebert D, Touquet Lagrange D, Pilloux Ludovic, B, Fournié GJ and MF Cesbron-Delauw (2014) A highly conserved Toxo1 haplotype directs resistance to toxoplasmosis and its associated caspase-1 dependent killing of parasite and host macrophage. PLoS Path. 10(4), e1004005. doi: 10.1371/journal.ppat.1004005

2. Mercier C and MF Cesbron-Delauw (2015) Toxoplasma secretory granules: one population or more? Trends Parasitol. 31: 60-71. doi: 10.1016/j.pt.2014.12.002

3. Lopez J., Bittame A, Massera C, Vasseur V, Effantin G, Valat A, Buaillon C, Allart S, Fox BA, Rommereim LM, Bzik DJ, Schoen G, Weissenhorn W, Dubremetz JF, Gagnon J, Mercier C, Cesbron-Delauw MF and N Blanchard (2015) Intravacuolar membranes regulate CD8 T cell recognition of membrane-bound Toxoplasma gondii protective antigen. Cell Reports 13: 2273-2286. doi: 10.1016/j.celrep.2015.11.001

4. Touquet B, Pellissier E, Cavailles P, Yi W, Bellini V, Mercier M, Cesbron-Delauw MF, Boumendjel A and D Aldebert (2018) High-content imaging assay to evaluate Toxoplasma gondii infection and proliferation: a multiparametric assay to screen new compounds. PLoS One 13(8):e0201678. doi: https://doi.org/10.1371/journal.pone.0201678.

5. Loeuillet C., Mondon A., Kamche S., Curri V., Boutonnat J., Cavaillès P. and MF Cesbron- Delauw (2019). Toxoplasma hypervirulence in the rat model parallels human infection and is modulated by the Toxo1 locus. Front. Cell. Infection Microbiol. 9 :13 doi: 10.3389/fcimb.2019.00134