Mitochondrial and metabolic adaptions in the innate immune system
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The mitochondrial electron transport chain (mETC) is a metabolic hub whose adaptations accompany fuel source fluctuations, stress responses, and innate immune signals to ensure optimal cellular functions. Innate immune cells tightly scale their core metabolism upon activation by innate immune receptors but the precise regulation of the mETC upon pathogen or dying cell recognition and its functional implications are currently poorly defined. In the laboratory, we are dissecting mETC rearrangements and the molecular events associated to the metabolic adaptations in response to innate immune receptors engagement. Conversely, we are evaluating the consequences of mETC adaptaions on the immune responses associated to infections, tolerance and anti-tumor responses. Finally we are characterizing mETC dysfunctions associated to hematopathologies.
Bibliography
Research articles in peer-reviewed journal:
Johan Garaude*,$, Rebeca Acín-Pérez*, Sarai Martínez-Cano, Michel Enamorado-Escalona, Matteo Ugolini, Estanislao Nistal-Villán, Sandra Hervás-Stubbs, Pablo Pelegrín Leif E. Sander, José A. Enríquez$, & David Sancho$. Mitochondrial respiratory-chain adaptations in macrophages contribute to antibacterial host defense. Nature Immunology. Doi 0.1038/ni.3509. (*Equal contributions) ($ jointly supervised the work, corresponding authors). Comet N.R., Aguiló J.I., Rathoré M.G., Catalán E., Garaude J., Uzé G., Naval J., Pardo J., Villalba M., Anel A. IFN-α signaling through PKC-θ is essential for anti-tumoral NK cell function. OncoImmunology. 2014 Nov 14;3(8):e948705 Kaminski S., Adjali O., Jacquet C., Garaude J., Keriel A., Lassaux L., Hipskind R.A., Sitbon S., Taylor N., and Villalba M. (2012) The protooncogene Vav1 regulates murine leukemia virus-induced T cell leukemogenesis. OncoImmunology. Aug 1;1(5):600-608 Garaude J., Kent A., van Rooijen N., & Blander J.M. (2012) Simultaneous targeting of toll- and nod-like receptors induces effective tumor-specific immune response. Sci. Transl. Med. 2012 Feb 8;4(120):120ra16. Cover article + Editors choice Torchinsky M., Garaude J., Martin A.P. and Blander J.M. (2009) Innate immune recognition of infected apoptotic cells directs T(H)17 cell differentiation . Nature, 458(7234):78-82 Related scientific publications Reviews, perspectives, author’s view and comments: Garaude J., (2013). Levée d’immunité innée dans le traitement des cancers. Med Sci (Paris). Nov;29(11):985-90 Anel A., Aguiló J.I., Catalán E., Garaude J., Rathore M.G., Pardo J., Villalba M. (2012). Protein Kinase C- (PKC-) in Natural Killer cell and Anti-Tumor immunity. Front Immunol. 2012;3:187. Villalba M., Rathore M.G., Lopez-Royuela N., Krzywinska E., Garaude J. and Allende-Vega N, (2012). From Tumor metabolic changes to tumor immune escape. Int J Biochem Cell Biol. Jan;45(1):106-13. Garaude J.* and Blander J.M.*, (2012). Attacking tumor cells with a dual ligand for innate immune receptors. Oncotarget. Apr;3(4):361-2. (*Corresponding authors) Garaude J.* and Blander J.M.*, (2012). ‘Flagellated’ cancer cells propel anti-tumor immunity. OncoImmunology. Sep 1;1(6):940-942. (*Corresponding authors) Garaude J. and Blander J.M., (2012). ICOStomizing immunotherapies with TH17. Sci. Transl. Med. Oct 27;2(55):55ps52. Torchinsky M., Garaude J. and Blander J.M. (2010) Infection and apoptosis as a joint inflammatory trigger. Curr Opin Immunol. Feb;22(1):55-62. Review More references, click on PubMed:
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Group leader
Johan GARAUDE Details
email: johan.garaude[a]inserm.fr Keywords
Innate immunity Metabolism Mitochondria Innate immune receptors Pathogen Cancer Mitochondrial electron transport chain Macrophages Dendritic cells Technical skills
Murine model of infections and cancer Flow cytometry Spectrophotometry Confocal microspopy Blue-native gel electrophoresis Mitochondria isolation Metabolomic and proteomic analysis 
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