Activation of intracellular innate immune sensors by viroses and self

Summary :

My lab, hosted at Institut Curie since 2010, is addressing how cells perform discriminate self, non-self and damaged-self at the intracellular level and how this impacts the immune system in health and disease. We study the mechanisms of intracellular detection of viruses in the nucleus, with a focus on the cGAS-STING pathway. We also study how perturbations of the structural integrity of the nucleus impact immune defenses and functions. Finally, my lab develops the applications of our findings in immuno-oncology. In this talk, I will present our recent developments related to these topics.
Selected references:
– Anvita Bhargava, Alice Williart, Mathieu Maurin, Patricia M. Davidson, Mabel Jouve, Matthieu Piel, Xavier Lahaye, Nicolas Manel. Inhibition of HIV infection by structural proteins of the inner nuclear membrane is associated with reduced chromatin dynamics. Cell Reports. 2021. doi: 10.1016/j.celrep.2021.109763
– Guilherme P.F. Nader, Sonia Agüera-Gonzalez, Fiona Routet, Matthieu Gratia, Mathieu Maurin, Valeria Cancila, Clotilde Cadart, Andrea Palamidessi, Rodrigo Nalio Ramos, Mabel San Roman, Matteo Gentili, Ayako Yamada, Alice Williart, Catalina Lodillinsky, Emilie Lagoutte, Catherine Villard, Jean-Louis Viovy, Claudio Tripodo, Jérôme Galon, Giorgio Scita, Nicolas Manel*, Philippe Chavrier*, Matthieu Piel*. Compromised nuclear envelope integrity leads to TREX1-dependent DNA damage and tumor cell invasion. Cell. 2021. doi: 10.1016/j.cell.2021.08.035
– Marius Döring, Kevin De Azevedo, Guillermo Blanco-Rodriguez, Francesca Nadalin, Takeshi Satoh, Matteo Gentili, Xavier Lahaye, Nilushi S De Silva, Cécile Conrad, Mabel Jouve, Mireille Centlivre, Yves Lévy, and Nicolas Manel. Single-cell analysis reveals divergent responses of human dendritic cells to the MVA vaccine. Science Signaling. 2021. doi: 10.1126/scisignal.abd9720
– Matthieu Gratia, Mathieu Paul Rodero, Cecile Conrad, Elias Bou Samra, Mathieu Maurin, Gillian I Rice, Darragh Duffy, Patrick Revy, Florence Petit, Russell C Dale, Yanick J Crow*, Mounira Amor-Gueret*, Nicolas Manel*. Bloom syndrome protein restrains innate immune sensing of micronuclei by cGAS. The Journal of Experimental Medicine. 2019. DOI: 10.1084/jem.20181329.
– Matteo Gentili, Xavier Lahaye, Francesca Nadalin, Guilherme F. P. Nader, Emilia Puig Lombardi, Solène Herve, Nilushi S. De Silva, Derek C Rookhuizen, Elina Zueva, Christel Goudot, Mathieu Maurin, Aurore Bochnakian, Sebastian Amigorena, Matthieu Piel, Daniele Fachinetti, Arturo Londoño-Vallejo, Nicolas Manel. The N-terminal domain of cGAS determines preferential association with centromeric DNA and innate immune activation in the nucleus. Cell Reports. 2019. DOI: 10.1016/j.celrep.2019.01.105.
– X. Lahaye, M. Gentili, A. Silvin, C. Conrad, L. Picard, M. Jouve, E. Zueva, M. Maurin, F. Nadalin, G.J. Knott, B. Zhao, F. Du, M. Rio, J. Amiel, A.H. Fox, P. Li, L. Etienne, C.S. Bond, L. Colleaux, N. Manel. NONO detects the nuclear HIV capsid to promote cGAS-mediated innate immune activation. Cell. 2018. DOI: 10.1016/j.cell.2018.08.062
– Silvin, A., Yu, C., Lahaye, X., Imperatore, F., Brault, J., Cardinaud, S., Becker, C., Kwan, W., Conrad, C., Maurin, M., Goudot, C., Marques-Ladeira, S., Wang, Y., Pascual, V., Anguiano, E., Albrecht, R., Iannacone, M., García-Sastre, A., Goud, B., Dalod, M., Moris, A., Merad, M, Palucka, A.K.*, Manel, N.* Constitutive resistance to viral infection in human CD141+ dendritic cells. Science Immunology. 2017. DOI: 10.1126/sciimmunol.aai8071
– X. Lahaye, T. Satoh, M. Gentili, S. Cerboni, A. Silvin, C. Conrad, A. Ahmed-Belkacem, E. C. Rodriguez, J.-F. Guichou, N. Bosquet, M. Piel, R. Le Grand, M. C. King, J.-M. Pawlotsky and N. Manel. Nuclear Envelope Protein SUN2 Promotes Cyclophilin-A-Dependent Steps of HIV Replication. Cell Reports. 2016. doi:10.1016/j.celrep.2016.03.074.
– Matteo Gentili, Joanna Kowal, Mercedes Tkach, Takeshi Satoh, Xavier Lahaye, Cécile Conrad, Marilyn Boyron, Bérangère Lombard, Sylvère Durand, Guido Kroemer, Damarys Loew, Marc Dalod, Clotilde Théry, Nicolas Manel. Transmission of Innate Immune Signaling by Packaging of cGAMP in Viral Particles. Science. 2015, 349:1232. doi: 10.1126/science.aab3628.