Integrative Biology of Emerging Infectious Diseases (IBEID) / Principal investigators
Lymphoid Tissue Development Unit
Institut Pasteur 25-28 rue du docteur Roux, 75015 Paris
Research area of the Unit
One of the goals of the Lymphoid Tissue Development Unit (LTD) are to decipher the role of symbiotic microbiota in the development of the immune system, in particular in the intestine where the microbiota is the most numerous and diverse. Recognition of microbes is performed by many types of cells that include leukocytes and stromal cells, the latter playing a fundamental role in the trafficking and organization of the immune cells. In addition, the LTD is engaged in identifying the bacterial symbionts present in mice and humans that modulate the immune state of the intestine and organs distal to the intestine, such as the lung and the skin, as well as those that influence the aging of the immune system. The LTD is evaluating the therapeutic value of symbiotic bacteria, probiotic bacteria and bacterial compounds against inflammatory pathologies. Major contributions of the LTD Unit include the demonstration of the critical role of innate cells in the development of secondary and microbe-induced lymphoid tissues, the discovery that particular symbiotic bacteria strongly induce the differentiation of pro-inflammatory T cells, and the discovery of innate lymphoid cells that pre-empt intestinal colonization of the gut.
Contribution to the programme
After birth, microbes colonize all surfaces of the human body, including the skin, mouth, digestive tract, upper respiratory tract and vagina. These symbionts establish a variety of relationships with their host that range from mutualism to parasitism. In the intestine, bacterial and archeal species complement the host in metabolic pathways for digestion and synthesis of essential vitamins, as well as in protection from pathogens. It has recently been shown how symbiotic bacteria induce a level of immune activity, termed "physiological inflammation", that protects the host from opportunistic infections, and at the same time compose a balanced community that prevents 'pathologic inflammation". Using cutting-edge technologies in metagenomics, microbiology and immunology, we aim to decipher the nature and the mechanisms of the "forced ménage à trois" between the host, its symbiotic microbiota, and emerging pathogens. Such knowledge will serve Public Health interests by generating novel preventive and therapeutic approaches against intestinal infectious and inflammatory disease.
References over the past 5 years
1. S. Sawa, M. Lochner, N. Satoh-Takayama, S. Dulauroy, M. Bérard, M. Kleinschek, D. Cua, J.P. Di Santo and G. Eberl. 2011. RORgt+ innate lymphoid cells regulate intestinal homeostasis by integrating negative signals from the symbiotic microbiota. Nat. Immunol., 12:320-326.
2. M. Lochner, C. Ohnmacht, L. Presley, P. Bruhns, M. Si-Tahar, S. Sawa and G. Eberl. 2011. Microbiota-induced tertiary lymphoid tissues aggravate inflammatory disease in the absence of RORgt and LTi cells. J. Exp. Med., 208:125-134.
3. S. Sawa, M. Cherrier, M. Lochner, N. Satoh-Takayama, H.J. Fehling, F. Langa, J.P. Di Santo and G. Eberl. 2010. Lineage relationship analysis of RORγt+ innate lymphoid cells. Science, 330:665-669.
4. G. Eberl. 2010. A new vision of immunity: homeostasis of the superorganism. Mucosal Immunology, 3:450-460.
5. D. Bouskra, C. Brézillon, M. Bérard, C. Werts, R. Varona, I. Gomperts Boneca, and G. Eberl. 2008. Lymphoid tissue genesis induced by commensals through NOD1 regulates intestinal homeostasis. Nature, 456:507-510.
6. M. Lochner, L. Peduto, M. Cherrier, S. Sawa, F. Langa, R. Varona, D. Riethmacher, M. Si-Tahar, J.P. Di Santo, and G. Eberl. 2008. In vivo Equilibrium of pro-inflammatory IL-17+ and regulatory IL-10+ Foxp3+ RORgt+ T cells. J. Exp. Med., 205:1381-1393.
7. N. Satoh-Takayama, C.A.J. Vosshenrich, S. Lesjean-Pottier, S. Sawa, M. Lochner, F. Rattis, J.J. Mention, K. Thiam, N. Cerf-Bensussan, O. Mandelboim, G. Eberl and J.P. Di Santo. 2008. Microbial flora drives interleukin 22 production in NKp46+ cells that provide innate mucosal immune defense. Immunity, 29:958-970.