Lena Alexopoulou PhD, HDR
Course and current status
1993 B.Sc. in Biology, University of Athens, Greece
1993-1998 Ph.D. in Molecular Biology, University of Athens, Greece. The experimental work was done at the Hellenic Pasteur Institute at the laboratory of George Kollias
1998 Postdoctoral Fellow, Laboratory of Richard Flavell, Yale University School of Medicine, Section of Immunobiology, New Haven, CT, USA
1999 Human Frontiers Science Program (HFSP) long-term fellowship
2002 Associate Research Scientist, Laboratory of Richard Flavell, Yale University, School of Medicine, Section of Immunobiology, New Haven, CT, USA
2004 Head of the Toll-like receptors in immunity Laboratory, Centre d’Immunologie de Marseille-Luminy (CIML), Marseille, France
2004 Senior Research Scientist (CR1, CNRS)
2009 Habilitation (HDR), Aix-Marseille University, France
2013 Director of Research (DR2, CNRS)
Scientific summary
My scientific interest is focused on dissecting the role of Toll-like receptors (TLRs) in the regulation of innate and adaptive immune responses. During my postdoctoral training I made several fundamental discoveries on the ligand specificity and biological function of TLRs by generating and analysing gene-targeted mice. The main findings were: TLR3 is a receptor for double stranded RNA and antiviral host defence, TLR1 senses bacterial lipoproteins and is important in human immune response, TLR5 detects flagellin and TLR7 is a sensor of viral infection through the detection of single stranded RNA. In 2004, I set up my research group at the Center of Immunology Marseille-Luminy in Marseille, France where we continued on dissecting the biological role of TLRs in antimicrobial host defence and inflammation. Recently, we uncovered the existence of an interplay between the nucleic acid-sensing TLRs (TLR7, TLR8, TLR9) that controls the regulation of their expression and function. Imbalance of this interplay has critical consequences since it can lead to the development of autoimmune diseases, such as systemic lupus erythematosus. Currently, we are using genetic approaches to provide better understanding on the implication of TLRs in sterile-inflammation.
Selected publications
Alexopoulou L, Holt AC, Medzhitov R and Flavell RA. Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature (2001) 413, 732-738.
Alexopoulou L, Thomas V, Schnare M, Lobet Y., Anguita J., Schoen R., Medzhitov R., Fikrig E., and Flavell R.A. Hyporesponsiveness to vaccination with Borrelia burgdorferi OspA in humans and in TLR1- and TLR2-deficient mice. Nat Med (2002) 8, 878-884.
Lund JM*, Alexopoulou L*, Sato A, Karow M, Adams NC, Gale NW, Iwasaki A and Flavell RA. Recognition of negative stranded RNA viruses by Toll-like receptor 7., Proc Natl Acad Sci USA (2004) 101, 5598-5603. *equal contribution
Wang T*, Town T*, Alexopoulou L*, Anderson JF, Fikrig F, and Flavell RA. Toll-like receptor 3 recognition of West Nile virus mediates viral entry into the brain causing lethal encephalitis. Nat Med (2004) 10, 1366-73. *equal contribution.
Feuillet V, Medjane S, Mondor I, Demaria O, Pagni PP, Gal·n JE, Flavell RA and Alexopoulou L. Involvement of TLR5 in the recognition of flagellated bacteria. Proc Natl Acad Sci U S A (2006) 103, 12487-92.
Pagni PP, Traub S, Demaria O, Chasson L, and Alexopoulou L. Contribution of TLR7 and TLR9 signaling to the susceptibility of MyD88-deficient mice to myocarditis. Autoimmunity. (2010) 43:275-87.
Demaria O, Pagni PP, Traub S, de Gassart A, Branzk N, Murphy AJ, Valenzuela DM, Yancopoulos GD, Flavell RA and Alexopoulou L. TLR8 deficiency leads to autoimmunity in mice. J Clin Invest. (2010) 120: 3651-62.
Alexopoulou L, Desnues B, Demaria O. Toll-like receptor 8: the awkward TLR. Med Sci (Paris) (2012) 28:96-102.
Traub S, Demaria O, Chasson O, Serra F, Desnues B, Alexopoulou L. Sex bias in susceptibility to MCMV infection: implication of TLR9. PLoS One (2012) 7:e45171.
Desnues B, Macedo AM, Roussel-Queval A, Bonnardel J, Henri S, Demaria O, and Alexopoulou L. TLR8 on dendritic cells and TLR9 on B cells restrain TLR7-mediated spontaneous autoimmunity in C57BL/6 mice. Proc Natl Acad Sci U S A (2014) 111:1497-502.
Desnues B, Macedo AB, Ordoñez-Rueda D, Roussel-Queval A, Malissen B, Bruhns P, Malissen M, and Alexopoulou L. The transcriptional repressor Gfi1 prevents lupus autoimmunity by restraining TLR7 signaling. Eur J Immunol (2016) 46: 2801-2811.
