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. Belloy M*, Schmitt BAM*, Marty FH, Paut C, Bassot E, Aïda A, Alis M, Zahm M, Chaubet A, Garnier H, Flores-Aguilar T, Roitg E, Gutierrez-Loli R, Allart S, Ecalard R, Boursereau R, Ligat G, Gonzalez-Dunia D, Blanchard N, Suberbielle E. Toxoplasma gondii infection and chronic IL-1 elevation drive hippocampal DNA double-strand break signaling, leading to cognitive deficits. Nat Neurosci. 2025 Aug 21. doi: 10.1038/s41593-025-02041-x.

2. Guemas E, Coppée R, Ménard S, du Manoir M, Nsango S, Makaba Mvumbi D, Nakoune E, Eboumbou Moukoko CE, Bouyou Akotet MK, Mirabeau TY, Manguin S, Malekita Yobi D, Akiana J, Kouna LC, Mawili Mboumba DP, Voumbo-Matoumona DF, Otam AL, Rubbo PA, Lombart JP, Kwanai E, Cohen O, Iriart X, Ayong L, Lekana-Douki JB, Ariey F, Berry A. Evolution and spread of Plasmodium falciparum mutations associated with resistance to sulfadoxine-pyrimethamine in central Africa: a cross-sectional study. Lancet Microbe. 2023 Dec;4(12):e983-e993. doi: 10.1016/S2666-5247(23)00211

3. Pignata A, Frieser D, Gonzalez-Fierro C, Hsiao CH, Engelenburg HJ, Alis M, Fijalkow I, Cazaentre V, Nozeran L, Miranda-Capet R, Dufourd E, Vermeulen T, Aida A, Le Coz C, Van Gisbergen K, BLANCHARD N, Hamann J, Smolders J, Liblau RS*, Masson F*. CD4+ Trm sustain the chronic phase of auto-immune neuroinflammatory disease. Sci Transl Med. 2025 Jul 23;17(808):eadp8109. doi: 10.1126/scitranslmed.adp8109.

4. Porte R, Belloy M, Audibert A, Bassot E, Aïda A, Alis M, Miranda-Capet R, Jourdes A, van Gisbergen KPJM, Masson F, Blanchard N. Protective function and differentiation cues of brain-resident CD8+ T cells during surveillance of latent Toxoplasma gondii infection. Proc Natl Acad Sci U S A. 2024 Jun 11;121(24):e2403054121. doi: 10.1073/pnas.2403054121.

5. 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 Rep. 2019 Jun 11;27(11):3254-3268.e8. doi: 10.1016/j.celrep.2019.05.051.