Unité de Biologie des Infections
Département Biologie Cellulaire et Infection
A number of viral, bacterial, and protozoan pathogens have in common the ability to actively invade a mucosa and cross the blood-brain barrier (BBB) and materno-fetal barrier (MFB). The objective of our group is the deciphering of the molecular mechanisms underlying microbial targeting and crossing of these host barriers. Building on the expertise we have acquired on the model microorganism Listeria monocytogenes, which is able to invade a mucosa and cross the BBB and the MFB, we broaden our investigations to a series of other microorganisms with a similar tropism, including bacteria such as group B streptococci, and viruses such as enteroviruses, flaviviruses and alphaviruses.
In vivo, ex vivo and in vitro approaches and molecular and cell biology techniques are combined to (i) study at the whole organism, tissue and cell levels microbial targeting and crossing of host barriers, (ii) identify the corresponding microbial and host determinants mediating these effects and (iii) study the host response to infection at the barrier level. For each class of pathogens and approach, we compare the phenotypes of clinically invasive and non-invasive isolates to ensure the consistency of the results.
In vivo models of infections are used, in combination with real-time imaging techniques including two-photon and spinning disk confocal microscopy and bioluminescence imaging, for in vivo tracking of fluorescent or bioluminescent microorganisms, respectively. This allows the real time imaging of the actual breaching of host barriers. Magnetic resonance imaging is also used for detecting the ensuing development of parenchymal lesions in the central nervous system and the feto-placental unit in living animals.
We have also set up experimental tools for studying the BBB and the MFB in vitro and ex vivo. In addition to classical mucosal barrier models, primary cell culture techniques that allow reproducing in vitro on microfilters the choroid plexus epithelial barrier and the brain microvascular endothelial barrier at the BBB level, as well as the placental and amniotic barriers at the MFB level are now available for experimental infection in different rodent species. Choroid plexus tissue explants, isolated brain microvessels, placental and amniotic tissue explants as well as intestinal explants can also be cultured and infected ex vivo, as well as infected in a dynamic context better mimicking the in vivo situation (microperfusion of microdissected tissue explants, and artificial fluid flow on cells grown in laminar fluid flow chambers).
By integrating these complementary techniques representative of the emerging “Tissular Microbiology” discipline and molecular and cell biology approaches, we wish to gain a better understanding of the molecular mechanisms underlying microbial translocation across mucosal barriers and microbial access to the central nervous system and the feto-placental unit. This will hopefully lead to the identification of novel medically relevant host-microbial interactions. The identified molecular players might then be exploited for designing new therapeutic approaches aimed at inhibiting microbial access to the central nervous system and the fetus, as well as at transferring molecules of interest across the BBB and the MFB. Overall, our research should also lead to a better comprehension of the basic cell biology of host barriers.
We are looking for highly motivated individuals with a strong background in one or more of the following or related fields:
- Cell biology
For questions or applications please contact Marc Lecuit: firstname.lastname@example.org