We investigate the molecular mechanisms regulating innate immune signalling in health and disease. A central question of our research is how pattern recognition receptors (PRRs), including Toll-like receptors (TLRs) and RIG-I-like receptors (RLRs), distinguish nucleic acids of pathogenic origin from harmless self-derived molecules to mount effective immune responses while maintaining immune homeostasis and preventing tissue damage.
Our research combines innate immunology, virology, RNA biology and extracellular vesicle research. We are particularly interested in endogenous mechanisms regulating innate immune signalling, virus–host interactions and extracellular vesicles as mediators of intercellular communication and a source of disease-associated biomarkers.
Mechanisms regulating innate immune signalling
Pattern recognition receptors (PRRs) detect pathogen-associated and danger-associated molecular patterns (PAMPs and DAMPs) and initiate signalling pathways that coordinate antiviral defence and broader immune responses. Because these pathways also respond to endogenous ligands, their activity must be tightly regulated to ensure efficient host defence while preventing inappropriate immune activation and tissue damage. We study how endogenous RNA species, RNA modifications and other physiological factors regulate innate immune signalling. In previous work, we identified a ribosomal RNA-derived endogenous RIG-I ligand and demonstrated that infection-induced processing of cellular RNAs contributes to antiviral immune activation (Jung et al., Nucleic Acids Research 2020; Steinberg et al., Viruses 2021). We further showed that RNA modifications influence immune recognition by the endosomal RNA sensors TLR7 and TLR8 (Jung et al., PLoS One 2015; Nicolai et al., IJMS 2022)
Current projects investigate how endogenous nucleic acid species contribute to immune homeostasis and how their dysregulation promotes inappropriate immune activation. We further investigate physiological mechanisms that fine-tune innate immune signalling, including regulation by endogenous cellular metabolites.
Virus–host interactions and RNA biology
Viruses have evolved diverse strategies to evade, suppress and exploit host immune responses. We are particularly interested in how hepatotropic viruses interact with cellular RNA regulatory pathways and innate immune signalling networks. Using hepatitis B virus and hepatitis D virus as model systems, we investigate how viral infection reshapes antiviral immune responses, RNA metabolism and the function of cellular RNA-binding proteins. These studies build on our previous work on innate immune recognition during HDV infection, virus-induced immune activation and extracellular vesicle-mediated immune signalling (Jung et al., World Journal of Gastroenterology 2020; Jung et al., Matters 2020; Altstetter et al., Cells 2021).
A current focus is how viruses manipulate cellular RNA regulatory pathways to alter the availability, processing and recognition of endogenous immune-stimulatory nucleic acids. In this context, we are also interested in the contribution of endogenous retroelements to innate immune signalling and antiviral defence. Through collaborative projects, we further investigate how these molecular mechanisms contribute to immune dysregulation in autoimmune disease.
Extracellular vesicles in infection and disease
Extracellular vesicles (EVs) are released by virtually all cell types and carry molecular information reflecting the state of their cell of origin. During viral infection, EVs can transfer viral and infection-induced host molecules, thereby contributing to intercellular communication and modulation of innate immune responses.
We investigate EVs both as mediators of immune communication and as a source of disease-associated biomarkers. We previously demonstrated that HDV-infected cells release immune-activating extracellular vesicles and established methods to separate extracellular vesicles from virions, enabling a more precise analysis of EV-mediated functions (Jung et al., Matters 2020; Jung et al., Journal of Extracellular Vesicles 2020). Building on these findings, we investigate EV-associated molecular cargo as biomarkers of viral infection and disease progression while continuing to develop improved methods for EV isolation, characterization and RNA analysis.
Method development
Method development is an integral part of our research. We establish and apply approaches for the analysis of immunomodulatory RNAs, virus-EV separation, EV purification and EV-associated molecular profiling. These methods support our mechanistic studies and provide opportunities for collaborative projects in infection biology, immunology and biomarker research.
