How does the interaction between intestinal microbiota and the immune system affect health and diseases?

Markus Geuking, PhD

The microbiota has been shown to be implicated in a range of immune-mediated disorders including inflammatory bowel disease, autoimmunity, and allergy. Therefore, altering the composition or function of the microbiota is a promising therapeutic approach to modulate immune responses involved in disease. Because T helper cells are involved in both immune adaptations to colonization and pathologic processes in disease, the lab focuses on the interaction of the microbiota with T helper cells.

The team uses germ free mice in combination with genetically modified commensal species to interrogate whether and how the microbiota can modulate T helper cell responses. This allows for carefully controlled and defined experiments to study how the microbiota modulates T helper cell response, but also how, in return, T helper cell responses directed at the microbiota impact on the microbiota at the level of transcriptional or metabolic activity and microbiota composition.

These are important parameters that need to be defined to be able to rationally design therapies that involve use of the microbiota as a tool to therapeutically modulate immune responses in disease.

This project develops genetically modified microbes as tools to study antigen-specific T helper cell responses in gnotobiotic situations with precisely defined species composition of the microbiota. This allows the use of state-of-the-art technologies including intravital microscopy, next generation transcriptional profiling of individual sorted species, and immunophenotyping using flow and mass cytometry to be used as readouts.