Research Projects
Host-pathogen interaction in the modulation of immune responses
Several bacterial species of the microbiota are essential to the equilibrium of the immune system. This is perfectly illustrated by a recent discovery of our team. Among the numerous bacteria living in our bowel, one of them is responsible for the differentiation and proliferation of a particular lymphocyte population (white blood cells), known as « regulatory », which controls the excess of immune response. When the number of these bacteria decreases, the number of regulatory lymphocytes does the same, which may thus draw to the development of an inflammatory bowel disease. One hypothesis of our team is that such lymphocytes, induced by microbiota bacteria, are involved in the equilibrium or, at the opposite, in the imbalance of the immune response in other situations. Preliminary results obtained by our team suggest that Mycobacterium tuberculosis also induces such regulatory lymphocytes, which may thus weaken the anti-tuberculous immune response of the patients. In this context, our team has developed several years ago an in vitro model to study the immune response against the tuberculosis bacillus, and consequently to find out novel strategies to improve it. This model also enables the screening of novel drugs against the Tuberculosis bacilli, targeting the bugs in an in vitro environment mimicking their natural in vivo situation in infected patients. The control of these regulatory cells thus paves the way for novel venues of therapeutic developments, not only for inflammatory diseases, but potentially also for infectious diseases. Click here for more details
Viruses responsible for Gastroenteritis reproduce massively during infection, thus driving to digestive tissues damages and to disease onset. Their impact on human populations is huge and drives to death numerous children in developing countries. However, during evolution our species has partially adapted to virus by selecting genetic variations able to protect some individuals. Whatever viral strain responsible, a part of the population will be spared. This is what the team contributed to demonstrate. However, these genetic differences seem to also have an impact on the microbiota composition, and consequently on the regulatory lymphocyte population described above. The team is trying to understand whether an adaptation to a type of microorganism (enteric viruses) may have as indirect consequence a microbiota composition more favourable to the appearance of inflammatory diseases. In this case, a favourable genetic variation for a given situation might be unfavourable in another context. Click here for more details
The team’s work on the genetics of susceptibility to gastroenteritis virus leads to an explanation of the limited efficacy of rotavirus vaccines in some developing countries where these viruses kill a significant number of very young children. This makes it possible to envisage the development of a new global vaccination approach, not limited by the specific recognition of extracellular receptors essential for infection by vaccine strains. This original vaccination system uses a different approach based on the use of nucleic acid molecules encoding the viral antigens of interest for rotavirus vaccine strategy. This is based on a unique and precise knowledge of the relationships between the physico-chemical properties of supramolecular nucleic acid / Nanocarrier assemblies and their ability to deliver into cells and express an antigen while stimulating innate immunity to induce a robust adaptive response. Thus, depending on the chemical nature of the nucleic acid (RNA, DNA) encoding the viral antigen, the nanocarrier will be adapted to take the cellular internalisation pathways maximizing the presentation to the specific molecular sensors of the nucleic acid used. This leads to the expression of interferons and cytokines at the injection site, while expression of the antigen occurs at the same time, leading to the production of antibodies and lymphocytes specific for the antigen. Click here for more details
Staff
F. Altare DR, INSERM
J. Le Pendu, DR INSERM
B. Pitard, DR CNRS
F. Jotereau, PREM. Eméritat
N. Ruvoën-Clouet, MCU ONIRIS
E. Godefroy, Post-doctorant, CDD Inserm
T. Haudebourg, Post-Doctorant
G. Ada Da Silva, Doctorant
T. Ruggeri, Doctorant
L. Barbé, Doctorant
T. Colombani, Doctorant
L. Dallet, Doctorant
J. Allameddine, Doctorant
A. Patinec, Doctorant
B. Le Moullac Vaidye, AI Inserm
J. Rocher, AJT Univ
E. Ekaza, IR CDD UNIV
A. Breiman, IR CDD CHU
S. Goude , AI INSERM
Main publications
– Nyström K, Le Moullac-Vaidye B, Ruvoën-Clouet N, Le Pendu J. Shared human/rabbit ligands for rabbit hemorrhagic disease virus. Emerg. Infect. Dis., 2012, 18: 518-519.
– Beilvert F, Tissot A, Langelot M, Mevel M, Chatin B, Lair D, Magnan A, Pitard B. DNA/amphiphilic block copolymer nanospheres reduce asthmatic response in a mouse model of allergic asthma. Hum Gene Ther. (2012)
– Hu L, Crawford SE, Czako R, Cortes-Penfield NW, Smith DF, Le Pendu J, Estes MK, Prasad BV. Cell attachement protein VP8* of a human rotavirus specifically interacts with A-type histo-blood group antigen. Nature (2012)
– Deknuydt F, Roquilly A, Cinotti R, Altare F, Asehnoune K. An in vitro model of mycobacterial granuloma to investigate the immune response in brain-injured patients. Crit Care Med. (2013)
– Ruvoën-Clouet, N., Magalhaes, A., Silva, L., Breiman, A., Ceu, F., David, L., Le Pendu, J. Increase in GII.4 norovirus host-spectrum by CagA+ Helicobacter pylori infection. J Infect Dis, (2014)
– Caddy S, Breiman A, Le Pendu J*, Goodfellow I*. Genogroup IV and VI Canine Noroviruses Interact with Histo-Blood Group Antigens. J. Virol. (2014)
– Imbert-Marcille B-M, Barbé L, Dupé M, Le Moullac-Vaidye B, Besse B, Peltier C, Ruvoën-Clouet N, Le Pendu J. A FUT2 gene common polymorphism determines resistance to rotavirus A of the P[8] genotype. J Infect Dis. (2013)
– Le Pendu J, Nyström K, Ruvoën-Clouet N. Host-pathogen co-evolution and glycan interactions. Curr. Op. Virol. (2014)
– Sarrabayrouse G, Bossard C, Chauvin JM, Jarry A, Meurette G, Quévrain E, Bridonneau C, Preisser L, Asehnoune K, Labarrière N, Altare F, Sokol H, Jotereau F. CD4CD8αα lymphocytes, a novel human regulatory T cell subset induced by colonic bacteria and deficient in patients with inflammatory bowel disease. PLoS Biol. (2014)
– Nyström, K., Abrantes, J., Lopes, A.M., Le Moullac-Vaidye, B., Marchandeau, S., Rocher, J., Ruvoën-Clouet, N., Esteves, P.J., Le Pendu, J. Neofunctionalization of the Sec1 α1,2fucosyltransferase paralogue in leporids contributes to glycan polymorphism and resistance to Rabbit Hemorrhagic Disease Virus. PLoS Pathogens (2015).
– Breiman, A., Lopez-Robles, M-D., de Carné Trécesson, S., Echasserieau, K., Bernardeau, K., Drickamer, K., Imberty, A., Barillé-Nion, S., Altare, F., Le Pendu, J. Carcinoma-associated fucosylated antigens are markers of the epithelial state and can contribute to cell adhesion through CLEC17A (Prolectin). Oncotarget (2016)
– Habrant D, Peuziat P, Colombani T, Dallet L, Gehin J, Goudeau E, Evrard B, Lambert O, Haudebourg T and Pitard B. Design of ionizable lipids to overcome the limiting step of endosomal escape : Application in the intracellular delivery of mRNA, DNA and siRNA. J Med Chem. (2016)
– Le Moigne V, Rottman M, Goulard C, Barteau B, Poncin I, Soismier N, Canaan S, Pitard B, Gaillard JL and Hermann JL. Bacterial phospholipases C as vaccine candidate antigens against cystic fibrosis respiratory pathogens: The Mycobacterium abscessus model. Vaccine. (2015)
Imprimer
