IMPRINT is a 2 year project funded by the European Commission under a
Marie Skłodowska-Curie Individual Fellowship. The main aim of IMPRINT is to uncover how the gut microbiota in early life trains the immune system to respond to infection in adulthood.
Humans acquire a complex community of intestinal microorganisms in early life (gut microbiota), which helps development of the immune system, and which may reduce risk of inflammatory disease. However, these complex microbiota-immune interactions in early life are underexplored and their subsequent influence on susceptibility to infection remains unknown. The Eberl lab in the Institut Pasteur recently reported that a temporary intestinal inflammatory state, termed the ‘weaning reaction’, occurs in mice during a specific window in early life (2-4 weeks) in response to the rapid diversification of the gut microbiota. During weaning, the gut microbiota and its metabolites induce a sub-type of T regulatory cells in the intestine (RORγt+ Tregs) which mediate immune tolerance throughout life. Suppression of the microbiota-induced weaning reaction suppresses RORγt+ Tregs and heightens susceptibility to immunopathology such as allergy and colitis in adulthood. However, it is unknown how the weaning reaction influences the later susceptibility and response to infection. IMPRINT will investigate how the gut microbiota influences the immune system in early life to regulate the response to infection in adulthood. Using mice, this project will evaluate the impact of suppressing the weaning reaction on susceptibility to Citrobacter rodentium infection in adulthood. Next, immune cell depletion models will be used to examine whether microbiota-induced immune cells during weaning influence susceptibility to C. rodentium infection in adulthood. Finally, metagenomics, metabolomics and add-back experiments will be performed to identify specific bacteria or metabolites that promote induction of specific immune cells during weaning and modulate subsequent susceptibility to C. rodentium infection. By combining metagenomics and metabolomics with intestinal immunology, IMPRINT poses potential to uncover insights into early-life microbiota-immune interactions and the pathogenesis of infectious disease.
Throughout the period of the IMPRINT project, a number of public engagement activities will take place to educate the general public and other stakeholders in the importance outcomes of the project.
On 30th September 2022, Dr. Ruairi Robertson participated in European Researchers Night, a European-wide evening of public engagement with science. In Paris, this was held in the Espace des sciences Pierre-Gilles de Gennes, in the 5th arrondissement. More than 200 people attended the event and engaged in various activities including presentations, science quizzes, scientist "speed-dating" and hands-on laboratory demonstrations. As part of the event, basic principles of the IMPRINT project were demonstrated to the public including imaging of live microorganisms under a microscope, displaying microscopy images of intestinal tissue and explanations of the gut microbiome and infant immune system.