2-to-3-yr POST-DOCTORAL POSITION / NEUROIMMUNOLOGY & PARASITOLOGY
Team ‘Eukaryotic Pathogens: Inflammation, T cell immunity and Chemoresistance’
Dr Nicolas Blanchard
Toulouse Institute for Infectious and Inflammatory Diseases (INFINITy)
Background
Neuroinflammation is a hallmark of many brain diseases, including Alzheimer’s disease (AD). Neuroinfllammation can be triggered by persistent brain infections such as the one caused by the Toxoplasma gondii (T. gondii) parasite. We and others have shown that latent T. gondii infection, which affects ~30% of the global population, has been linked to various neurological disorders (1) and can accelerate AD trajectory (in prep). Current anti-parasitic drugs can eliminate the disease’s active tachyzoite stage but are largely ineffective against cyst-forming bradyzoites in neurons, which maintain chronic infection. Neuronal MHC I presentation (2) and brain-resident CD8+ T cells are crucial for controlling T. gondii parasites in the brain (3), but the ability of CD8+ T cells to recognize and target bradyzoite-infected neurons is limited due to reduced MHC I antigen presentation.
Our recent work (Gutierrez-Loli et al. in prep) revealed that bradyzoite-infected neurons fail to upregulate the antigen presentation machinery upon IFN-γ stimulation, suggesting an immune evasion strategy. Evidence suggests that such immune evasion is driven by parasite-secreted factors inducing epigenetic silencing of MHC genes, a mechanism reminiscent of tumor immune escape.
The goal of the ANR project DEFEND is to investigate and neutralize the mechanisms allowing T. gondii latent stages to escape CD8+ T cell immune surveillance. We will address 3 specific aims:
(i) identify the parasite effectors that prevent bradyzoite-infected neurons to present antigens to CD8+ T cells via MHC I molecules and unravel their mechanisms of action ;
(ii) investigate the impact of epigenetic modulators on T. gondii chronic brain parasite load ;
(iii) evaluate the therapeutic potential of epigenetic modulators to mitigate T. gondii-mediated neurological dysfunction, in particular the acceleration of Alzheimer’s disease.
The post-doctoral researcher will work on one or a combination of these projects, using controlled experimental settings that enable us to study T. gondii infection in vivo and in vitro.
Context of the laboratory and position details
Our team is hosted at Toulouse Institute for Infectious and Inflammatory Diseases (INFINITy), a research Centre affiliated with Inserm, CNRS and University of Toulouse. Infinity provides a stimulating environment to perform state-of-the-art research in immunology and infectious diseases, with cutting-edge on-site technological facilities. Research teams at Infinity host international trainees, ranging from undergraduate students to postdocs. Seminars and lab meetings are held in English. Infinity is located in Toulouse, a dynamic and attractive city in the Southwest of France, ~1-hr away from Paris by plane.
The post-doctoral fellow will work in the context of an ANR-sponsored project (PRC DEFEND 2025-2029). Net salary will be adjusted depending on experience, starting at 2330 € / mo, including health benefits. The position is expected to start between Nov 2025 and May 2026.
Candidate profile
The postdoctoral fellow should be highly self-motivated, at ease with team work and able to independently organize his/her workload. Prior knowledge in neuroimmunology and/or infectious diseases, as well as research experience in transcriptomics and/or flow cytometry and/or mouse behavioral studies, would be beneficial, but is not mandatory. International candidates are strongly encouraged to apply. Applicants are invited to email a CV, a short statement of research interests and future goals + the names & contact information of 2 references to N. Blanchard : [email protected]. Deadline: Sep 30th 2025
On-site interviews of short-listed candidates may be organized.
References
- Belloy M, Schmitt BAM, Marty FH, Paut C, Bassot E, Aida A, et al. Toxoplasma gondii infection and chronic IL-1 elevation drive hippocampal DNA double-strand break signaling, leading to cognitive deficits. Nature neuroscience. 2025. Epub 2025/08/22.
- Salvioni A, Belloy M, Lebourg A, Bassot E, Cantaloube-Ferrieu V, Vasseur V, et al. Robust Control of a Brain-Persisting Parasite through MHC I Presentation by Infected Neurons. Cell reports. 2019;27(11):3254-68 e8. Epub 2019/06/13.
- Porte R, Belloy M, Audibert A, Bassot E, Aida A, Alis M, et al. 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;121(24):e2403054121. Epub 2024/06/05.
