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. 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.
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.
Emerging paradigm shifts
Not long ago, innate immunity was viewed as an immediate response system that relies on primitive and non-specific activation mechanisms. With the discovery that innate immune receptors rather sense alterations in their environment and the notion that innate immune activation ultimately regulates adaptive immune responses, the discipline of innate immunity has become one of the most dynamic fields in life sciences. This is also reflected by a number of paradigm shifts emerging over the last few years. First, innate immune receptors were initially thought to mainly detect foreign microbial molecules during infections. Now it is evident that innate immune mechanisms sense both exogenous and endogenous molecules and that innate immune mechanisms also serve to surveil tissue health.
Second, a number of innate immune receptors are expressed in all somatic cell types and can therefore act in cell autonomous defense. Thus, innate immune mechanisms function beyond classical immune cells and the concept of an immune sensory system is therefore not restricted to the classical immune cell subsets. Third, innate immune responses do not function in a uniform manner but rather depend on the specific cellular and tissue contexts in which they occur and vary in quantity and quality. Fourth, innate immunity has motile cellular elements which can act independently, and immune activation is functionally connected to other systems such as the metabolic system and the central nervous system. These paradigmatic shifts substantially extend previous concepts of innate immunity.
The Excellence Cluster takes an interdisciplinary approach to elucidating the principles of the immune sensory system. In conjunction with experts in classical sensory systems, we aim at resolving the spatiotemporal regulation of sensory input on the receptor level, where clear similarities to classical sensory systems exist. With respect to neurobiology, although the nervous system is clearly not involved in performing the immune sensory signal processing, its role is similar to that of the metabolic system (e.g. FOXO signaling), which is to provide additional information (e.g. endocannabinoid signaling) that is integrated in the immune sensory signal processing. Furthermore, if it comes to permanent dysregulation of the immune sensory system in disease, uncontrolled inflammation can contribute to neuroinflammation and neurodegeneration. In both of these areas of neurobiology, there is strong expertise in Bonn.