Areas of Research: Our major goal is to understand how immune cells (T, B and mononuclear cells) differentiate into protective long-lasting effector cells to develop novel immune-based therapies against microbial pathogens and tumors.
Immune effector cell differentiation & protective host responses against microbial pathogens and tumors in vivo
Microbial pathogens invasion usually triggers potent host immune responses, however efficient protection and pathogen killing require the presence of effector cells and combinations of inflammatory signals that are ill-defined in most infections and during cancers.
Our work therefore focuses on precisely defining these events using mouse models and when possible patient samples. Specifically, we investigate (i) the inflammatory signals and related pathways, and innate immune cells that regulate CD8 T cell differentiation, and (ii) the cross-talks between memory T cells and innate immune cells during infections as well as tumor progression and (iii) the protective immune response against malaria. Immune cells we focus on include monocytes, macrophages, dendritic cells and T and B lymphocytes. We use various models of infections in mice, namely the bacteria Listeria monocytogenes, the Vesicular Stomatitis virus and Murine Cytomegalovirus and various murine Plasmodium parasites. We take advantage of a range of advanced fluorescent-tracer based methodologies to monitor immune cells in situ. We conduct cell transfer experiments and take advantage of novel genetically modified mouse models in which dynamic cell functions can be monitored and/or in which functional subsets of immune cells can be selectively eliminated.
Overall, the goal of my laboratory is to improve our fine understanding of the factors that orchestrate antimicrobial and antitumoral host protective immune responses in vivo. We believe that our work will contribute to better immune cell-mediated preventive and therapeutic strategies.
Current laboratory members:
Tere Williams, Ph. D. Student
Jamie Moore, M. D./Ph. D. Student
Marie Boutet, Ph. D., Postdoctoral fellow
Mandy Shu Shien Chin, Ph. D., Postdoctoral fellow
Laurent Chorro, Ph. D., Postdoctoral fellow
A. Original Articles (Selected):
- Subramaniam K.S., Spaulding E., Ivan E., Mutimura E., Kim R.S., Liu X., Dong C., Feintuch C.M., Zhang X., Anastos K., Lauvau G. and Daily J.P. 2015. The T cell inhibitory molecule BTNL2 is upregulated in mild Plasmodium falciparum infection and is protective during experimental cerebral malaria. J Infect Dis, Apr 15. pii: jiv217.
- Chandrabos C.*, M’Homa Soudja S. *, Weinrick B., Gros M., Frangaj A., Rahmoun M., Jacobs W.R. Jr. and G. Lauvau. 2014. The p60 and NamA Autolysins from Listeria monocytogenes Contributes to Host Colonization and Induction of Protective Memory. Cell Microbiol, 17(2):147-63.
- Anne L. Ruiz,, Saidi M’Homa Soudja, Cyril Deceneux, Grégoire Lauvau and Julien C. Marie. 2014. NK1.1+ CD8+ T Cells Escape TGFbeta control and Contribute to Early Microbial Pathogen response. 2014. Nature Communication, 5:5150.
- Soudja M’Homa S., Jacob E., Chandrabos C., M. Veenstra, Palliser D. and G. Lauvau. 2014. Memory T cell-derived IFN-g instructs potent innate cell activation for protective immunity. Immunity, 40(6):974-88.
- Soudja M’Homa S., Ruiz A. L., Marie J. C., and G. Lauvau.2012.Inflammatory monocytes switch on memory CD8+ T and innate NK lymphocytes during microbial pathogens invasion. Immunity, 37(3):549-62.
- Narni-Mancinelli E., Soudja M’Homa S., Crozat K., Dalod M., Gounon P., Geissmann F. and G. Lauvau. 2011. Inflammatory monocytes and neutrophils are licensed to kill during Memory responses in vivo. PLoS Pathogens, Vol 7(12):e1002457.
- Campisi L., S. SoudjaM’Homa, N. Cagnard, J. Cazareth, D. Bassand, A. Lazzari, E. Narni-Mancinelli, F. Brau, N. Glaichenhaus, F. Geissmann and G. Lauvau. 2011. Splenic CD8a+ Dendritic Cells Undergo Rapid Programming by Cytosolic Bacteria and Inflammation to Induce Protective CD8 Memory. Eur J Immunol, 41(6):1594-605.
- Bajénoff M., Narni-Mancinelli E., Brau F., and G. Lauvau. 2010. Visualizing early splenic memory CD8+ T cells reactivation against intracellular bacteria. PLoS One. 5:11524.
- Auffray C.*, D. K. Fogg*, E. Narni-Mancinelli*, B. Senechal, C. Touillet, N. Saederup, J. Leemput, K. Bigot, L. Campisi, M. Abitbol, T. Molina 1, I. Charo, D. A. Hume, A. Cumano, G. Lauvau and F. Geissmann. 2009. CX3CR1+ CD115+ CD135+ common macrophage/DC precursor (MDP) and the role of CX3CR1 in their response to inflammation. J Exp Med, 206: 595-606.
- Narni-Mancinelli E., L. Campisi, D. Bassand, J. Cazareth, P. Gounon, N. Glaichenhausand G. Lauvau. 2007. Memory CD8+ T cells mediate antibacterial immunity via CCL3 activation of TNF/ROI+ phagocytes. J Exp Med, 204: 2075-2087.
- Auffray, C., D. K. Fogg, Meriem Garfa, G. Elain, O. Join-Lambert, S. Kayal, S. Sarnacki, A. Cumano, G. Lauvau and F. Geissmann.2007. Patrolling blood monocytes that monitor blood vessels and tissues for damage and infection. Science, 317, 666-70.
- Muraille, E.*, E. Narni-Mancinelli*, P. Gounon*, D. Bassand, N. Glaichenhaus, L. L. Lenz, and G. Lauvau. 2007. Cytosolic Expression of SecA2 is a Prerequisite for Long-Term Protective Immunity. Cell Microbiol, 9, 1445-1454.
- Muraille, E., R. Giannino, P. Guirnalda, I. Leiner, S. Jung, E. G. Pamerand G. Lauvau. 2005. Distinct in vivo dendritic cell activation by live versus killed Listeria monocytogenes. Eur J Immunol, 35:1-9.
- Lauvau, G*., S. Culina*, B. Gubler, and P.M. van Endert. 2004. Calreticulin promotes folding of functional HLA class I molecules in vitro. J Biol Chem, 279:54210-54215.
- Lauvau, G.*, S. Vijh*, P. Kong, T. Horng, K. Kerksiek, N. Serbina, R.A. Tuma, and E.G. Pamer. 2001. Priming of memory but not effector CD8 T cells by a killed bacterial vaccine. Science, 294:1735-1739.
- Lauvau, G*., B. Gubler*, H. Cohen, S. Daniel, S. Caillat-Zucman, and P.M. van Endert. 1999. Tapasin enhances assembly of transporters associated with antigen processing-dependent and -independent peptides with HLA-A2 and HLA-B27 expressed in insect cells. J Biol Chem, 274:31349-31358.
- Lauvau, G., K. Kakimi, G. Niedermann, M. Ostankovitch, P. Yotnda, H. Firat, F.V. Chisari, and P.M. van Endert. 1999. Human transporters associated with antigen processing (TAPs) select epitope precursor peptides for processing in the endoplasmic reticulum and presentation to T cells. J Exp Med, 190:1227-1240.
B. Review Articles/Chapters:
- Lauvau G., Loke P., Holh T.M. Monocyte Mediated Defense Against Pathogenic Microbes. Seminars in Immunology, In press.
- Lauvau G., S. M’Homa Soudja. 2015. Mechanisms of Memory T Cell Activation and Effective Immunity. Adv Exp Med Biol, 850:73-80.
- Lauvau G. 2015. PI3-kinase, the key for bugs to get in? J Exp Med, 9;212(2):127.
- Lauvau G., L. Chorro, E. Spaulding, S. M’Homa Soudja. 2014. Inflammatory Monocyte Effector Mechanisms. Cellular Immunology, S0008-8749(14)00125-7.
- Lauvau G., M’Homa Soudja S., Chorro L. 2013. T cell Memory. Encyclopedia of Medical Immunology, I.R. Mackay, N.R. Rose (eds.), Springer Science, DOI 10.1007/978-0-387-84828-0.
- Geissmann F., C. Auffray, R. Palframan, C. Wirrig, A. Ciocca, L. Campisi, E. Narni-Mancinelli, and G. Lauvau. 2008. Blood monocytes: distinct subsets, how they relate to dendritic cells, and their possible roles in the regulation of T cell responses. Immunology and Cell Biology, 86:398-408.
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