Focus
We are interested in the how individual members of the gut microbiota influence the host immune system, how they promote colonization resistance and how they interact with the host during health and disease.
Introduction
The gut microbiota plays an integral part in shaping the host immune system and amongst its many functions, helps to protect the host from pathogens. How individual bacterial species contribute to colonization resistance is still poorly understood. For now, the foremost commensal associated with colonization resistance in the gut, as well as at distal mucosal sites, is the Clostridium-related commensal segmented filamentous bacteria (SFB). SFB is a common commensal in many vertebrates where it colonizes the host at the time of weaning and strongly stimulates secretory IgA responses, innate defenses and a potent Th17 response. SFB is a thereby a key member of the microbiota that potently shapes the immunological milieu of the host and influences immune reactivity. In the lab, we are interested in deciphering the novel interaction of SFB with intestinal epithelial cells at the molecular level, how this interaction fosters physiological inflammation in the host, and how the SFB-mediated immune activation results in enhanced resistance to pathogens in and outside of the gut. Aside a better basic understanding of the unique cross talk between this medically-relevant microbe and the host, our long-term goals is to develop a novel vaccine delivery platform against enteropathogens.
Research objectives
We currently focus our investigations of the host-microbiota interaction on the unique cross talk between the commensal SFB and the host. SFB intimately attaches to intestinal epithelial cells, leading to actin recruitment at the site of contact. This interaction is key for the stimulatory potential of SFB and likely involves the conditioning of the immune cells by SFB-mediated stimulation of epithelial cells. For one, we aim to characterize the tight interaction of SFB with the intestinal epithelial cell using a number of proteomic, molecular and immunological approaches. We also aim to better understand how epithelial cells respond to SFB challenge and to identify and characterize host factors involved in the activation of the host immune system. At the same time, we are interested in the molecular mechanisms, and to what extent, SFB can mediate colonization resistance in and outside of the gut. In addition, we aim to establish genetic manipulation techniques for SFB for mutagenesis studies and to express foreign antigens in order to test SFB as a vaccine delivery platform.
Main publications
- Nkamba I, Mulet C, Dubey GP, Gorgette O, Couesnon A, Salles A, Moya-Nilges M, Shima T, Umesaki Y, Nigro G, Krijnse-Locker J, Berard M, Cerf-Bensussan N, Sansonetti PJ, Schnupf P. Intracellular offsprings released from SFB filaments are flagellated. Nature Microbiology. In press.
- Schnupf P, Gaboriau-Routhiau V, Sansonetti P, Cerf-Bensussan N. Segmented filamentous bacteria, Th17 inducers and helpers in a hostile world. Current Opinion in Microbiology. 2017, 35: 100-109.
- Vonaesch P, Campbell-Valois FX, A Dufour, Sansonetti P, Schnupf P. Shigella flexneri modulates stress granule composition and inhibits stress granule aggregation. Cellular Microbiology. 2016. Jul;18(7):982-97
- Schnupf P, Gaboriau-Routhiau V, Gros M, Friedman R, Moya-Nilges M, Nigro G, Cerf-Bensussan N, Sansonetti PJ. Growth and host interaction of mouse Segmented Filamentous Bacterium in vitro. Nature. 2015. Apr 2;520(7545):99-103.
- Schnupf P, Gaboriau-Routhiau V, Cerf-Bensussan N. Host-interactions with Segmented Filamentous Bacterium: An unusual trade-off that drives the post-natal maturation of the gut immune system. Seminars in Immunology. 2013. 25(5):342-51.
