Interfakultäres Institut für Mikrobiologie und Infektionsmedizin

Laufende Projekte AG Frick

Impact of the intestinal microbiota on induction of regulatory B cells

Jan Kevin Maerz, PhD Student

In general, B cells positively regulate adaptive immune responses by the production of antibodies and thus facilitate optimal CD4+ T-cell activation. Additionally, B cells modulate the innate immune system via presentation of antigens and the secretion of immune-modulating cytokines. Furthermore, a specific subset of B cells (Bregs) exhibit immunosuppressive functions and can also negatively regulate the immune response in mouse models of autoimmune diseases. Thereby the intestinal microbiota plays a critical role for the induction of different B cell phenotypes either by direct or indirect interaction.

In order to clarify the influence of the intestinal microbiota composition on B cell-mediated immune responses and the role of Bregs in supporting immune homoeostasis, we focus on the immune system activating capacities of two completely sequenced bacterial strains in vitro and in vivo.

Influence of the intestinal microbiota on the outcome of type 1 diabetes (T1D)

Brigitte Beifuss, PhD Student

In several autoimmune diseases, among them Diabetes Type 1, auto antigen presentation occurs and results in an immune response against host antigens, thus destroying host tissue, e.g pancreatic β- cells. This project aims to monitor the molecular mechanisms of this mislead immune response and how to interfere or prevent Diabetes type 1 by alteration of the microbiota or its components.

Work on strategies of symbiotic and pathobiontic commensals to colonize the gut and how they survive in the healthy and inflamed intestine.

Anna Lange, PhD Student

Pathobionts like E. coli colonize the gut in very low amounts and symbiotic commensals in high abundance the must use different metabolic pathways to grow and reside in the gut ecosystem. Based on genome sequencing certain pathways are investigated.

Immunomodulatory properties of E. coli Nissle flagella

Thomas Hagemann, PhD student and Lena Michaelis, PhD Student

E. coli Nissle is a probiotic bacterial strain which is known to promote intestinal homeostasis. As many other bacteria, this strain contains a flagellum, making it a motile bacterium. The flagellum is built up of the FliC protein and we are interested how the E. coli Nissle flagella in general, and FliC in specific, help to promote E.coli Nissle mediated intestinal homeostasis. Answering this question might allow to elucidate future therapeutic approaches using isolated FliC protein in patients with Inflammatory Bowel Diseases.

Commensal bacterial surface structures as potential immunomodulatory agents?

Alex Steimle, PhD student and Jan Kevin Maerz, PhD student

Not only the bacterial flagelly, but also other bacterial surface compounds are potent immunomodulatory agents. We therefore screen for other structures, derived from certain commensals which might be able to restore intestinal homeostasis and/or promote healing of damaged colonic tissue, like it is observed in Inflammatory Bowel Disease Patients.

How the intestinal microbiota triggers host cathepsin S activities

Alex Steimle, PhD student

Cathepsin S is a lysosomal protease that is involved in the regulation of MHC-II surface expression and therefore in activation of CD4+T cells. This biological function makes Cathepsin S a promising drug target for the treatment of autoimmune diseases which are associated with pathologically disturbed CD4+ T cell activation. Therefore, chemical Cathepsin S inhibitors are widely discussed to be prospective therapeutics. However, we propose that host cathepsin S activities are regulated by the intestinal microbiota and that certain commensal bacteria prevent from uncontrolled Cathepsin S activation, leading to a stop of pathological CD4+ T cell activation.

Influence of Cathepsin B on intestinal homeostasis

Alex Steimle, PhD student

Not only Cathepsin S, but also Cathepsin B seems to be regulated by commensal bacteria in the intestine. We are therefore interested in the biological effects of Cathepsin B activity regulation on a local level (the intestine) and probable systemic effects on the host.

How the microbiota manages to regulate dendritic cell function

Alex Steimle, PhD student and Brigitte Beifuss, PhD student

Dendritic cells play an outstanding role in mediating microbiota-triggered immune responses. We have identified a certain regulatory protein in dendritic cells which provides surprisingly widespread effects on the dendritic cell phenotype and its T cell activation potential, making this protein a potential key regulatory factor in the progress of microbiota-dependent autoimmune diseases

Commensals and their impact on Th17 immune responses

Alex Steimle, PhD student, Johanna Klees, MD student and Alex Birg, M.Sc. student

Th17 immune responses are known to contribute to the progress auf autoimmune diseases. We therefore have a closer look, how distinct commensal bacteria differentially promote or prevent Th17 responses on the host, on a systemic and molecular level.

Bioinformatical analysis of distinct dendritic cell maturation states

Dendritic cells exist in different maturation/activation states which in turn affects tolerogenicity or strong immune response in IBD. By employing proteomics and bioinformatics we are investigating the protein expression profiles of distinct DC maturation states and upstream effectors underlying the phenotypical and disease relevant properties of distinct DC maturation states.

Immune signaling during infection in a novel animal model: Galleria melonella

Raphael Parusel, PhD student

The invertebrate greater waxmoth Galleria mellonella represents a novel animal model in infection biology. According to the 3R strategy (reduction, replacement, refinement) we want to promote Galleria mellonella as a potential invertebrate alternative to mice by establishing defined molecular read-outs. Since to date less is known about Galleria mellonella immune defense mechanisms and detailed signaling pathways, we focus on basic research on these issues.

Establishment of Galleria mellonella as a host model to study gut microbe interactions and the maintenance of gut homeostasis.

Anna Lange, PhD Student

Due to strict regulations concerning animal grants and for ethical reasons we seek to establish an substitute invertebrate host model, which can be used to analyze the effect of certain microbes both commensals and pathogens on the innate immune system of Galleria mellonella. As the innate immune system is highly conversed among mammals and insects such substitute models can be used prior to experiments with mammals.