Prof. Dr. Alexander N.R. Weber
Innate immunity employs Toll-like receptors (TLRs) and Nod-like receptors (NLRs), both families of so-called pattern recognition receptors (PRRs), to detect a variety of different exogenous and endogenous insults. Exogenous insults include bacteria, viruses and fungi.. Upon engagement of their cognate microbe-derived molecular ligands, PRRs initiate distinct intracellular signalling pathways via receptor-proximal adaptor molecules, and subsequent NF-kB- and IRF-mediated gene transcription activates immediate innate immune responses and primes adaptive immunity. Since the discovery of human TLRs in 1997, other families of mainly cytosolic pattern recognition receptors (PRRs) have been described, for example, the RIG-I-like receptors (RLRs), Nod/NACHT-LRR-like receptors (NLRs) and AIM2-like receptors (ALRs). Together with TLRs, these PRR fulfill the important function of immune surveillance in the innate immune system and mark the first line of immune detection for most microbes. Apart from their role in infection, PRR have also been shown to be vital sensors of the various microbiomes found in different body sites, e.g. the intestine, and to be involved in sensing endogenous danger signals, e.g. accumulated metabolites or tissue breakdown products. As the initial recognition of microbes and endogenous danger signals by PRR has a profound influence on the timing, scale, type and extent of all subsequent innate and adaptive immune responses, PRR are nowadays recognized as pivotal immune regulatory molecules.
Our research focus is dedicated to this important group of sensors. Although our understanding of PRR biology is steadily advancing, the principles of ligand recognition and intracellular signaling still remain poorly known. Little is also know about the differences of these signaling pathways in different human primary cell types or in normal versus transformed cells. Additionally, the functional and epidemiological significance of PRR single-nucleotide polymorphisms (SNPs) remains largely unknown.
Not only can functional PRR SNPs provide insights into PRR biology but in the dawning an age of “personalized medicine” understanding genetic variation at the levels of PRR and immune recognition appears vital. To address some of the open questions surrounding this area of innate immunity, our laboratory is taking a unique approach: