Group leader: Jean-Pierre Levraud

NeuroInfection & Immunity

In brief

The team « NeuroInfection and Immunity » studies central nervous system infections, which are often lethal or cause severe neurological deficits in newborns. The host inflammatory response attacks microbes, but may also be highly deleterious to the brain. We use transparent zebrafish larva to visualize virus infected cells in real-time by microscopy, as well as the immune response simultaneously. We analyze the consequences of viral encephalitis as well as the impact of inflammation itself on the nervous system development.
The team, which is doubly affiliated to CNRS and Institut Pasteur, established itself in 2021 in the new Saclay building.

Our team is studying host-pathogen interactions during infections of the central nervous system (CNS), with the aim of improving the outcome of infectious encephalitis. We also have a broader interest in neuroinflammation in a wider context. We use the transparent zebrafish larva as our main model of study.

Main projects:

  • Spatial dynamics of a neuroinvasive virus (such as Sindbis virus or Herpes Simplex Virus) and the interferon (IFN) response it elicits. Routes and rates of SINV entry in the brain and the spinal cord. Cell-to-cell propagation in the CNS. Cell types producing IFN, and responding to it, in the CNS. Impact of infection on survival and functions of neurons and other cells of the CNS.
  • CNS repair after a viral infection. Development of recombinant viruses allowing controlled termination of infection. Identification of genes induced during the repair phase and comparison with sterile injury models. In vivo functional testing of common repair genes.
  • Deconstructing the negative impact of IFN-mediated neuroinflammation. Description of the repertoire of ISGs (IFN-stimulated genes) in the different CNS cell types. CRISPR-based screen of individual ISG impact on brain development and function.
  • Development of models of bacterial encephalitis/meningitis.

Selected publications

  • LEVRAUD J.-P., Jouneau L., Briolat V., Laghi V., Boudinot P. IFN-stimulated genes in zebrafish and humans define an ancient arsenal of antiviral immunity. Journal of Immunology 203: 3361 (2019). DOI: 10.4049/jimmunol.1900804
  • Hernández P.P., Strzelecka P.M., Athanasiadis E.I., Hall D., Robalo A.F., Collins C.M., Boudinot P., Cvejic A.*, LEVRAUD J.-P.* Single-cell transcriptional analysis reveals ILC-like cells in zebrafish. Science Immunology, 3:eaau5265 (2018). DOI: 10.1126/sciimmunol.aau5265
  • Aguado L.C., Schmid S., May J., Sabin L.R., Panis M., Blanco-Melo D., Shim J.V., Sachs D., Cherry S., Simon A.E., LEVRAUD J.-P., tenOever B. RNase III nucleases from diverse kingdoms serve as antiviral effectors. Nature, 547:114 (2017). DOI: 10.1038/nature22990
  • Passoni G., Langevin C., Palha N., Mounce B., Briolat V., Affaticati P., De Job E., Joly J.-S., Vignuzzi M., Saleh M.-C., Herbomel P., Boudinot P., LEVRAUD J.-P. Imaging of viral neuroinvasion in the zebrafish reveals that Sindbis and Chikungunya viruses favour different entry routes. Disease Models and Mechanisms, 10 :847 (2017). DOI: 10.1242/dmm.029231
  • Mounce B.C., Poirier E.Z., Passoni G., Simon-Loriere E., Cesaro T., Prot M., Stapleford K.A., Moratorio G., Sakuntabhai A., LEVRAUD J.-P., M. Vignuzzi. Interferon-Induced Spermidine-Spermine Acetyltransferase and Polyamine Depletion Restrict Zika and Chikungunya Viruses. Cell Host & Microbe, 20 : 137-177 (2016). DOI: 10.1016/j.chom.2016.06.011
  • Nguyen-Chi M., Laplace-Builhe B., Travnickova J., Luz-Crawford P., Tejedor G., Phan Q. T., Duroux-Richard I., LEVRAUD J-P., Kissa K, Lutfalla G., Jorgensen C., Djouad F. Identification of polarized macrophage subsets in zebrafish. eLife, 4:e07288 (2015). DOI: 10.7554/eLife.07288
  • Kasher P.R., Jenkinson E.M., Briolat V., Gent D., Morrissey C., Zeef L.A., Rice G.I., LEVRAUD J.-P, Crow Y.J. Characterization of samhd1 morphant zebrafish recapitulates features of the human type I interferonopathy Aicardi-Goutières syndrome. Journal of Immunology 194:2819 (2015). DOI: 10.4049/jimmunol.1403157
  • LEVRAUD J.-P., Palha N., Langevin C., Boudinot P. Through the looking glass : witnessing host-virus interactions in zebrafish (review). Trends in Microbiology, 22 : 490-497 (2014). DOI: 10.1016/j.tim.2014.04.014

Team leader

Members

  • Levraud JP, Rawls JF, Clatworthy AE. Using zebrafish to understand reciprocal interactions between the nervous and immune systems and the microbial world. J Neuroinflammation. 2022 Jun 28;19(1):170. doi: 10.1186/s12974-022-02506-x
  • Banerjee P, Joly P, Jouneau L, Jaszczyszyn Y, Bourge M, Affaticati P, Levraud JP, Boudinot P, Joly JS. Molecular and Cellular Analysis of the Repair of Zebrafish Optic Tectum Meninges Following Laser Injury. Cells. 2022 Jun 24;11(13):2016. doi: 10.3390/cells11132016
  • Kraus A, Huertas M, Ellis L, Boudinot P, Levraud JP, Salinas I. Intranasal delivery of SARS-CoV-2 spike protein is sufficient to cause olfactory damage, inflammation and olfactory dysfunction in zebrafish. Brain Behav Immun. 2022 May;102:341-359. doi: 10.1016/j.bbi.2022.03.006
  • Rutherford HA, Clarke A, Chambers EV, Petts JJ, Carson EG, Isles HM, Duque-Jaramillo A, Renshaw SA, Levraud JP, Hamilton N. A zebrafish reporter line reveals immune and neuronal expression of endogenous retrovirus. Dis Model Mech. 2022 Apr 1;15(4):dmm048921. doi: 10.1242/dmm.048921
  • Laghi V, Rezelj V, Boucontet L, Frétaud M, Da Costa B, Boudinot P, Salinas I, Lutfalla G, Vignuzzi M, Levraud JP. Exploring Zebrafish Larvae as a COVID-19 Model: Probable Abortive SARS-CoV-2 Replication in the Swim Bladder. Front Cell Infect Microbiol. 2022 Mar 11;12:790851. doi: 10.3389/fcimb.2022.790851
  • Rességuier J, Levraud JP, Dal NK, Fenaroli F, Primard C, Wohlmann J, Carron G, Griffiths GW, Le Guellec D, Verrier B. Biodistribution of surfactant-free poly(lactic-acid) nanoparticles and uptake by endothelial cells and phagocytes in zebrafish: Evidence for endothelium to macrophage transfer. J Control Release. 2021 Mar 10;331:228-245. doi: 10.1016/j.jconrel.2021.01.006
  • Widziolek M, Janik K, Mojzesz M, Pooranachandran N, Adamek M, Pecio A, Surachetpong W, Levraud JP, Boudinot P, Chadzinska M, Rakus K. Type I interferon-dependent response of zebrafish larvae during tilapia lake virus (TiLV) infection. Dev Comp Immunol. 2021 Mar;116:103936. doi: 10.1016/j.dci.2020.103936
  • Stressmann FA, Bernal-Bayard J, Perez-Pascual D, Audrain B, Rendueles O, Briolat V, Bruchmann S, Volant S, Ghozlane A, Häussler S, Duchaud E, Levraud JP, Ghigo JM. Mining zebrafish microbiota reveals key community-level resistance against fish pathogen infection. ISME J. 2021 Mar;15(3):702-719. doi: 10.1038/s41396-020-00807-8
  • Colucci-Guyon E, Rifflet A, Saint-Auret S, da Costa A, Boucontet L, Laval T, Prehaud C, Blanchard N, Levraud JP, Boneca IG, Demangel C, Guenin-Macé L. Spatiotemporal analysis of mycolactone distribution in vivo reveals partial diffusion in the central nervous system. PLoS Negl Trop Dis. 2020 Dec 2;14(12):e0008878. doi: 10.1371/journal.pntd.0008878
  • LEVRAUD J.-P., Jouneau L., Briolat V., Laghi V., Boudinot P. IFN-stimulated genes in zebrafish and humans define an ancient arsenal of antiviral immunity. Journal of Immunology 203: 3361 (2019). DOI: 10.4049/jimmunol.1900804
  • Hernández P.P., Strzelecka P.M., Athanasiadis E.I., Hall D., Robalo A.F., Collins C.M., Boudinot P., Cvejic A.*, LEVRAUD J.-P.* Single-cell transcriptional analysis reveals ILC-like cells in zebrafish. Science Immunology, 3:eaau5265 (2018). DOI: 10.1126/sciimmunol.aau5265
  • Aguado L.C., Schmid S., May J., Sabin L.R., Panis M., Blanco-Melo D., Shim J.V., Sachs D., Cherry S., Simon A.E., LEVRAUD J.-P., tenOever B. RNase III nucleases from diverse kingdoms serve as antiviral effectors. Nature, 547:114 (2017). DOI: 10.1038/nature22990
  • Passoni G., Langevin C., Palha N., Mounce B., Briolat V., Affaticati P., De Job E., Joly J.-S., Vignuzzi M., Saleh M.-C., Herbomel P., Boudinot P., LEVRAUD J.-P. Imaging of viral neuroinvasion in the zebrafish reveals that Sindbis and Chikungunya viruses favour different entry routes. Disease Models and Mechanisms, 10 :847 (2017). DOI: 10.1242/dmm.029231
  • Mounce B.C., Poirier E.Z., Passoni G., Simon-Loriere E., Cesaro T., Prot M., Stapleford K.A., Moratorio G., Sakuntabhai A., LEVRAUD J.-P., M. Vignuzzi. Interferon-Induced Spermidine-Spermine Acetyltransferase and Polyamine Depletion Restrict Zika and Chikungunya Viruses. Cell Host & Microbe, 20 : 137-177 (2016). DOI: 10.1016/j.chom.2016.06.011
  • Nguyen-Chi M., Laplace-Builhe B., Travnickova J., Luz-Crawford P., Tejedor G., Phan Q. T., Duroux-Richard I., LEVRAUD J-P., Kissa K, Lutfalla G., Jorgensen C., Djouad F. Identification of polarized macrophage subsets in zebrafish. eLife, 4:e07288 (2015). DOI: 10.7554/eLife.07288
  • Kasher P.R., Jenkinson E.M., Briolat V., Gent D., Morrissey C., Zeef L.A., Rice G.I., LEVRAUD J.-P, Crow Y.J. Characterization of samhd1 morphant zebrafish recapitulates features of the human type I interferonopathy Aicardi-Goutières syndrome. Journal of Immunology 194:2819 (2015). DOI: 10.4049/jimmunol.1403157
  • LEVRAUD J.-P., Palha N., Langevin C., Boudinot P. Through the looking glass : witnessing host-virus interactions in zebrafish (review). Trends in Microbiology, 22 : 490-497 (2014). DOI: 10.1016/j.tim.2014.04.014