Pamela Schnupf

Website: https://www.institut-necker-enfants-malades.fr/index.php?menu=team&rubric=teamtabs&idfac=schnupf
ORCID: 0000-0003-4292-1257
Twitter: @pamela_schnupf

General Scientific Interest

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 structural and molecular details in the unique life-cycle of SFB as well as the novel interaction of SFB with intestinal epithelial cells, 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 that leads to colonization resistance. As little tools are available for SFB, we aim to increase the toolbox and succeed in establishing genetic manipulation techniques to be able to do mutagenesis and ultimately test SFB as a novel vaccine delivery platform.

For the manipulation of our favorite bacterium, we use a hypoxic chamber that allows for highly controlled levels of oxygen or anaerobic conditions.

Top 5 publications

1. Nkamba I, Mulet C, Dubey GP, Gorgette O, Couesnon A, Salles A, Moya-Nilges M, Jung V, Gaboriau-Routhiau V, Guerrera IC, 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. 2020. Jan; 5(1):34-39.

2. Schnupf P and Sansonetti PJ. Shigella pathogenesis: new insights through advanced methodologies. Microbiol Spectrum. 2019. 7(2): BAI-0023-2019.

3. Schnupf P, Gaboriau-Routhiau V, Cerf-Bensussan N. Modulation of the gut microbiota to improve innate resistance. Current Opinion in Immunology. 2018. 54:137-144.

4. Schnupf P, Gaboriau-Routhiau V, Sansonetti PJ, Cerf-Bensussan N. Segmented filamentous bacteria, Th17 inducers and helpers in a hostile world. Current Opinion in Microbiology. 2017. 35: 100-109.

5. Vonaesch P, Sansonetti PJ, Schnupf P. Immunofluorescence analysis of stress granule formation after bacterial challenge of mammalian cells. JoVE. 2017 (125), e55536, doi:10.3791/55536.

Dernières publications sur HAL :