Marc  LECUIT
Microbes and host barriers Unit
Institut Pasteur 25-28 rue du docteur Roux, 75015 Paris
 
Research area of the Unit
 
The group Microbes and host barriers studies the biology of infectious diseases, with a particular focus on the molecular bases of host, tissue and cell tropisms of human microbial pathogens. The group is especially interested in understanding how microbes target and cross host barriers such as mucosal barriers, the blood-brain barrier and the placental barrier. It studies two model microorganisms, Listeria monocytogenes and Group B streptococcus, which are both major causes of central nervous system and neonatal infections; and an emerging virus, Chikungunya, which it has shown to be associated with central nervous system and neonatal diseases. The team combines in vitro, ex vivo and in vivo approaches and follows an integrative and multidisciplinary strategy that makes use of cultured cell lines, primary cells, tissue explants and animal models, molecular techniques in the fields of microbiology, virology and cell biology, as well as "humanized" genetically engineered animals that take into account the species specificity of human pathogens.
Another area of investigation is the discovery of emerging pathogens and of the infectious origin of orphan human diseases, in the framework of the PathoDisc program set up by the Institut Pasteur and a network of clinicians and veterinarians.
 
Contribution to the program
 
The contribution of the MHB group to the program will be threefold:
- First, it will continue to study the molecular mechanisms underlying Listeria monocytogenes and group B streptococcus pathogenesis. These two deadly bacterial pathogens that lead to central nervous system infection, notably in the neonatal context, are associated with an extremely high morbidity and mortality even when an appropriate antimicrobial therapy is administered, urging for novel and more effective therapeutics. In this context, the group has assigned itself the following objectives (i)to understand the detailed molecular mechanisms underlying microbial crossing of host barriers, which is a defining step of infection; (ii) to gain a better basic knowledge on the biology of host barriers, which are key for the host physiology and many pathological states, from infections to metastasis; and finally (iii) to identify targets for developing blocking strategies to antagonize host barrier crossing, and conversely, transfer molecules of interest across host barriers.
- Second, it will continue and expend its work on emerging microbes, with Chikungunya being the major pathogen studied in this context, and the possibility in the future to broaden investigations to other emerging microbes representing a threat to Public Health and for which basic knowledge on their pathogenic properties and disease mechanisms are critically lacking.
- Third, this group will also be involved in the identification and characterization of novel human and animal pathogens, in the framework of the PathoDisc initiative.
 
References over the past 5 years
 
1. Nikitas G, Deschamps C, Disson O, Niault T, Cossart P, Lecuit M. Transcytosis of Listeria monocytogenes across the intestinal barrier upon specific targeting of goblet cell accessible E-cadherin. J. Exp. Med. 2011;208(11):2263-77.
 
2. Tazi A, Disson O, Bellais S, Bouaboud A, Dmytruk N, Dramsi S, Mistou M-Y, Khun H, Mechler C, Tardieux I, Trieu-Cuot P, Lecuit M, Poyart C. The surface protein HvgA mediates Group B streptococcus hypervirulence and meningeal tropism in neonates. J Exp Med. 2010 Oct 25;207(11):2313-22.
 
3. Schilte C, Couderc T, Chrétien F, Sourisseau M, Gangneux N, Guivel-Benhassine F, Gruber A, Tschopp J, Higgs S, Michault A, Arenzana-Seisdedos F, Colonna M, Schwartz O, Lecuit M, Albert M. Type I IFN controls chikungunya virus via its action on non-hematopoetic cells. J Exp Med. 2010 Feb 15;207(2):429-42.
 
4. Toledo-Arana A, Dussurget O, Nikitas G, Sesto N, Guet-Revillet H, Balestrino D, Loh E, Gripenland J, Tiensuu T, Vaitkevicius K, Barthelemy M, Vergassola M, Nahori M-A, Soubigou G, Régnault B, Coppée J-Y, Lecuit M, Johansson J, Cossart P. The Listeria transcriptional landscape from saprophytism to virulence. Nature. 2009 Jun 18;459(7249):950-6
 
5. Disson O, Grayo S, Huillet E, Nikitas G, Langa-VivesF, Dussurget O, Ragon M, Le Monnier A, BabinetC, Cossart P, Lecuit M. Conjugated action of two species-specific invasion proteins for fetoplacental listeriosis. Nature. 2008 Oct 23;455(7216):1114-8
 
6. Couderc T, Chrétien F,Schilte C, Disson O, Brigitte M, Guivel-Benhassine F, Touret Y, Barau G, Prévost MC, Schuffenecker I, Desprès P, Arenzana-Seisdedos F, Michault A, Albert ML, Lecuit M. A mouse model for Chikungunya infection: young age and inefficient type-I interferon signaling are risk factors for severe disease. PLoS Pathog, 2008. 4(2): p. e29
 
7. Gérardin P, Barau G, Michault A, Bintner M, Randrianaivo H, Choker G, Lenglet Y, Touret Y, Bouveret A, Grivard P, Le Roux K, Blanc S, Schuffenecker I, Couderc T, Arenzana-Seisdedos F, Lecuit M, Robillard PY. Multidisciplinary prospective study of mother-to-child chikungunya virus infections on the island of La Réunion. PLoS Medicine, 2008. 5(3): p. e60