Molecular Mucosal Immunology
The mammalian large intestine contains one of the densest microbial consortia found anywhere on the planet. While some of these microbes are genuinely beneficial, synthesizing vitamin K or helping to digest dietary fibre, this is typically also home to an array of opportunistic pathogens. Our research focuses on elucidating the mechanisms by which the mucosal immune system can control the abundance and pathogenicity of these microbes.
Our current research approach aims to continuously bridge between fundamental immunology research, microbial ecology, and clinical applications. On-going projects include:
Defining immunogenicity in the gut: While parenterally delivered antigen tends to induce broad T and antibody responses dependent on mismatch to self and presence of adjuvant, the rules at our mucosal surfaces seem to be more complex. Bacterial surface antigens are more strongly recognized than cytosolic components and particulate antigen seems to be required. However, the true nature of these determinants of mucosal immunogenicity remains unclear. We address this challenge using BCR and TCR knock-in mice, as well as heterologous expression of specific protein and glycan antigens in different bacterial species and different subcellular compartments.
Defining the role of capsular polysaccharides in resistance to intestinal IgA-mediated clearance of Enterobacteriaceae: In this project we characterize capsular polysaccharide structures and investigate the role of their expression on 1) the induction of intestinal IgA responses specific for surface glycan and protein structures and 2) the protective mechanisms of intestinal IgA targeting different surface glycans or protein structures. Fundamental knowledge from this project will be applied for the generation of mucosal vaccines which can decolonize opportunistic pathogens from the human and animal intestine.