Research Overview

The immune sensory organ

Like a classical sensory system, the innate immune system possesses an elaborate receptor interface to sense and discriminate a large variety of stimuli. We like to view the innate immune system as an immune sensory organ with its diverse immune sensing receptors, since this term lives up to the capacity of the innate immune system to sense its environment.

Great advances have been made in the discipline of innate immunity, one of the most dynamic fields in life sciences. At the core of innate immunity lie pattern recognition receptors (here: immune sensing receptors), most of which have been discovered within the last twenty years. Immune sensing receptors detect foreign microbial molecules or altered self-molecules from tissue damage. The activation of immune sensing receptors initiates defense and repair mechanisms that normally protect the host. However, dysregulation of these responses can cause a range of inflammatory diseases. With the recent discoveries that particular immune sensing receptors are present in most somatic cells and that the metabolic state and neuronal inputs are tightly integrated, innate immunity has developed beyond the boundaries of classical immunology.

In order to fine-tune immune sensing over the course of an immune reaction, from response to resolution, adaptation and memory, we propose a network immunoscience theory: Despite obvious differences in the anatomical architecture and functionality of cellular components between the immune system and the nervous system, the principal structure of both systems exhibit suprising analogies. Hence we propose that insight into the network topology of nervous systems and the application of this insight to immune functions will help to achieve a more comprehensive understanding of the global behaviour of the immune system. This will also facilitate both precise prediction and control of immune activities, i.e. precision immunology.

We have also come to realize that the dysregulation of the immune sensing system has a strong impact on many prevalent diseases in Western societies, such as atherosclerosis, metabolic syndrome, type 2 diabetes, neurodegeneration and cancer. Hence, there is a clear need to gain further mechanistic insights into the regulation of immune activation and to identify novel approaches for pharmacological interference.

All five programs together represent a truly collaborative approach of the applicants and the associated scientists, with every PI substantially contributing to more than one topic, and integrating additional contributing scientists as indicated, emphasizing the high degree of interdisciplinarity within the cluster. Moreover, within the different research areas of each program, tailored combinations of advanced collaborative approaches are used to address specific scientific questions.

To resolve the fundamental questions posed by the ImmunoSensation²
concept, the cluster relies on the unique and complementary
expertise of its members and their collaborative access to advanced
experimental designs.

The cluster has established a number of complementary scientific approaches since it last funding period, which are used to pertubate and characterize processes from the molecular level to entire organisms and multi-organism systems. Beyond the boundaries of classical immunology, the cluster encompasses expertise in related fields such as systems immunology and structural biology, and utilizes advanced tools and methods such as nanobody generation, Mass Spectrometry, protein crystallization, and more (see picture). These advanced scientific approaches will enable cluster members to design and adapt experimental settings which decode the specific regulatory immune circuits that are responsible for the functional connections between the level of immune sensing and the levels of response, resolution and memory.

The Cluster of Excellence addresses its concept by linking research on innate immunity at the University of Bonn with world-class expertise in neurobiology (German Center for Neurodegenerative Diseases, DZNE) and mathematics (Institute of Applied Mathematics). The University of Bonn, the Medical Faculty and the Life & Medical Sciences Institute (LIMES), have already established highly successful cross-faculty interactions, which have led to a number of important discoveries in the field of immune sensing, namely in inflammasome research, immunorecognition of nucleic acids, lectins and dendritic cells, local immune regulation in the liver and the gut, immune cell migration, the endocannabinoid system and the crossroad of metabolism and innate immunity. It is now evident that immune sensing is involved in many of the lifestyle-associated diseases of modern societies, such as atherosclerosis, metabolic syndrome and diabetes, neurodegeneration and cancer.