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.
Downstream of immune sensing receptor ligation, multiple layers of information processing and ‘decision making’ operate to finally recognize patterns of danger or damage, and to subsequently trigger the appropriate effector functions. Therefore, we prefer to use the term immune sensing for the detection of ligands on the receptor level, while the term pattern recognition includes downstream processing events. These considerations have led us to further postulate that immune sensing is tightly intertwined with the levels of response, resolution, adaptation and memory.
We further posit that immune active cues from the neuronal, metabolic and endocrine systems as well as from nutrition-, tissue- and microbiome-derived bioactive substances can modulate the immune sensory system at all four levels. According to our vision, immune circuit-aided perception by the immune sensory system allows it to adapt to its environment over time through continous adjustments of the sensitivity of immune surveillance and the quality of the immune response. Such finely-tuned immune decisions adjusted to the needs of whole organisms can be viewed as intelligent behaviour of the immune system. Conceptually, we therefore aim to decode the mechanisitic basis for such Immune Intelligence.
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.
ImmunoSensation2 focusses on
- the characterization of immune sensory receptors and immune sensing
- the identification of components involved in circuit regulation of immune homeostasis
- the application of mathematical modeling to understand the immune network regulation of systemic immune functions
- unraveling the pathogenesis of immune-mediated diseases through functional human immunogenomics
- delivering translational precision immunology
The scientific program of ImmunoSensation2 is designed to address key challenges in immunology, with an emphasis on innate immunity. While immune sensing is the common basis of all levels of an immune reaction and thus remains an important overarching topic of the scientific program, our goal now is to apply our current knowledge of the immune sensory system to the functional circuits that connect immune sensing, response, resolution, adaptation and memory. We postulate that these functional immune circuits form the basis of intelligent immune decisions and that their dysregulation contributes to immune-mediated disorders. Moreover, we hypothesize that functional immune circuits are an integral part of a network topology of the immune system. The research program with its specific research areas and topics has been selected to fill in some of the most important gaps of the proposed network topology of the immune system.
Program 1: The Mechanisms of Sensing
Program 2: Circuit Regulation of Sensing and Response
Program 3: Circuit Regulation of Sensing and Resolution
Program 4: Circuit Regulation of Sensing, Adaptation and Memory
Bridging Program: Biomathematics
Advanced collaborative research approach
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
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.
The immune system is essential for our health, yet its dysregulation is involved in the pathogenesis of many common diseases. With the concept of an immune sensory system, which integrates the sensing functions of immune and non-immune cells, ImmunoSensation2 has become one of the leading centers for immunological research (Bonn Center of Immunology). Our seminal contributions, especially in the field of innate immunity, include the identification of novel receptor ligands, a new second messenger, new paradigms of cell-to-cell communication, a new classification of macrophage activation, insights into immunopathogenesis of cancer, a new target to restore cognitive function, and the impact of Western diet on trained immunity.
Read more in our final report from the first funding period
(2012 - 2018).
Prizes & Awards
ImmunoSensation2 brings together renowned scientists with internationally outstanding reputations. Accordingly, the members of the Cluster of Excellence include recipients of various prestigious prizes and awards.
Laureates of the Gottfried Wilhelm Leibniz-Prize
- Prof. Gunther Hartmann & Prof. Christian Kurts (2011)
- Prof. Frank Bradke (2016)
- Prof. Eicke Latz (2018)
ERC Grant holders
- Prof. Eicke Latz (ERC Consolidator Grant, 2013)
- Prof. Katrin Paeschke (ERC Starting Grant, 2014)
- Prof. Bernardo Franklin (ERC Starting Grant, 2017)
- Prof. Elvira Mass (ERC Starting Grant, 2019)
- Prof. Carmen Ruiz de Almodóvar (ERC Consolidator Grant, 2019)
- Prof. Volker Busskamp (ERC Proof of Concept, 2021)
- Prof. Felix Meissner (ERC Consolidator Grant, 2022)
- Prof. Rayk Behrendt (ERC Consolidator Grant, 2022)
Emmy Noether Junior Research Groups
- Prof. Andreas Schlitzer (2015)
- Prof. Florian I. Schmidt (2017)
Laurates of the Heinz Maier Leibnitz-Prize
- Prof. Natalja Novak (2005)
- Prof. Elvira Mass (2020)
NRW Return awards
- Prof. Christoph Wilhelm (2014)
- Prof. Eva Kiermaier (2017)