Nicolas BLANCHARD

Information

Scientific interests and projects

General scientific interests
We study immune responses to Toxoplasma and Plasmodium infections, with a major interest on the implication of T cell responses in host protection and immunopathology. We focus on the molecular determinants of antigen presentation and T cell immunity to these two apicomplexan intracellular parasites.
More specifically, using mouse models of Toxoplasma infection, we have dissected the molecular bases of tachyzoite antigen processing and presentation by macrophages and DC. We have recently established that MHC I presentation of tachyzoite antigens by neurons is critical for durable parasite control in the brain during chronic toxoplasmosis. Another outcome of this work was to create a unique experimental system to study latency and encephalitis in the widely used C57BL/6 mouse model.
In the context of malaria infection, we have profiled the first malaria MHC class II immunopeptidome (i.e. the repertoire of peptides presented by MHC II on the surface of DC). We have shed light on the deleterious role of a subset of conventional DC (cDC1) in driving pathogenic CD4 T cell responses during severe malaria.

We foresee two activities within the Parafrap consortium:
1- in the context of chronic toxoplasmosis, elucidate how cyst-containing neurons, possibly via specific effectors, evade CD8 T cell recognition to allow the establishment of latency.

2- implement a ‘forward vaccinology’ approach based on Plasmodium falciparum immunopeptidome characterization. The goal is to identify and prioritize candidate antigens for a blood stage malaria vaccine.

Top 5 publications of the last 5 years

1. Salvioni A, Belloy M, Lebourg A, Bassot E, Cantaloube-Ferrieu V, Vasseur V, Blanié S, Liblau RS, Suberbielle E, Robey EA, Blanchard N. Robust control of a brain-persisting parasite through MHC I presentation by infected neurons. Cell Reports 2019 Jun 11;27(11):3254-3268.e8. doi: 10.1016/j.celrep.2019.05.051.

2. Bonnart C, Feuillet G, Vasseur V, Cénac N, Vergnolle N*, Blanchard N* (* = co-senior). Toxoplasma gondii infection promotes gut inflammation through Protease Activated Receptor 2 independently from IFNγ and TNFα. Parasite Immunol 2017 Nov;39(11). doi: 10.1111/pim.12489.

3. Draheim M, Wlodarczyk MF, Crozat K, Saliou JM, Alayi TD, Tomavo S, Hassan A, Salvioni A, Demarta-Gatsi C, Sidney J, Sette A, Dalod A, Berry A, Silvie O, Blanchard N. Profiling MHC II immunopeptidome of blood stage malaria reveals that cDC1 control the functionality of parasite-specific CD4 T cells. EMBO Mol Med 2017 Sep 21. pii: e201708123. doi: 10.15252/emmm.201708123.

4. Cebrian I, Croce C, Guerrero NA, Blanchard N*, Mayorga LS*. (* = co-senior). Rab22a controls MHC-I intracellular trafficking and antigen cross-presentation by dendritic cells. EMBO Rep. 2016 Dec;17(12):1753-1765. doi: 10.15252/embr.201642358.

5. Lopez J, Bittame A, Massera C, Vasseur V, Effantin G, Valat A, Buaillon C, Allart S, Fox BA, Rommereim LM, Bzik DJ, Schoehn G, Weissenhorn W, Dubremetz JF, Gagnon J, Mercier C, Cesbron-Delauw MF, Blanchard N. Intravacuolar membranes regulate CD8 T cell recognition of membrane-bound Toxoplasma gondii protective antigen. Cell Reports 2015 Dec 15, 13, 1–14. doi: 10.1016/j.celrep.2015.11.001.