A5022062058- Immune Response and Inflammation
- interferon and immune responses
- Immunotherapy and Immune Responses
- RNA Interference and Gene Delivery
- Immune Cell Function and Interaction
- Cytokine Signaling Pathways and Interactions
- Cytomegalovirus and herpesvirus research
- Virus-based gene therapy research
- Influenza Virus Research Studies
- Immune cells in cancer
- Herpesvirus Infections and Treatments
- Viral Infections and Vectors
- T-cell and B-cell Immunology
- Hepatitis C virus research
- Inflammasome and immune disorders
- Nanoplatforms for cancer theranostics
- CAR-T cell therapy research
- IL-33, ST2, and ILC Pathways
- Mosquito-borne diseases and control
- Systemic Lupus Erythematosus Research
- Respiratory viral infections research
- Multiple Sclerosis Research Studies
- Antimicrobial Peptides and Activities
- Oral microbiology and periodontitis research
- Hepatitis B Virus Studies
Medizinische Hochschule Hannover
2016-2025
Helmholtz Centre for Infection Research
2010-2019
Center for Experimental and Clinical Infection Research
2015-2019
Matrix Research (United States)
2019
Center of Molecular Immunology (Cuba)
2009-2013
Paul Ehrlich Institut
2011
University of Freiburg
2011
University of Basel
2011
Angiogenesis is a hallmark of malignant neoplasias, as the formation new blood vessels required for tumors to acquire oxygen and nutrients essential their continued growth metastasis. However, signaling pathways leading tumor vascularization are not fully understood. Here, using transplantable mouse model, we have demonstrated that endogenous IFN-beta inhibits angiogenesis through repression genes encoding proangiogenic homing factors in tumor-infiltrating neutrophils. We determined...
Objective The spondyloarthritides (SpA) are a group of rheumatic diseases characterized by ossification and inflammation entheseal tissue, the region where tendon attaches to bone. Interleukin‐23 (IL‐23) is involved in pathogenesis SpA acting on IL‐23 receptor (IL‐23R) expressed enthesis‐resident lymphocytes. Upon binding, CD3+CD4−CD8− tissue‐resident lymphocytes secrete IL‐17A IL‐22, leading inflammation, bone loss, ossification. Knowledge about remains fragmentary, contribution γ/δ T cells...
Significance The newest generation of small-molecule vaccine adjuvants aims at triggering specific receptors expressed by dendritic cells, the working horses our immune system. Unfortunately, owing to their small size, upon administration these molecules rapidly enter systemic circulation and cause inflammation. We report on a nanotechnology-based solution for this issue covalent ligation potent immunostimulatory molecule hydrogel nanoparticles. This approach allows lymph node-restricted...
Abstract Idiopathic pulmonary fibrosis (IPF) is a fatal disease with limited treatment options. In this study, we focus on the properties of airway basal cells (ABC) obtained from patients IPF (IPF-ABC). Single cell RNA sequencing (scRNAseq) bronchial brushes revealed extensive reprogramming IPF-ABC towards KRT17 high PTEN low dedifferentiated type. 3D organoid model, compared to ABC healthy volunteers, give rise more bronchospheres, de novo structures resembling lung developmental...
Type I IFN is a major player in innate and adaptive immune responses. Besides, it involved organogenesis tumor development. Generally, responses are amplified by an autocrine loop with IFN-beta as the priming cytokine. However, due to lack of sensitive detection systems, where how type produced vivo still poorly understood. In this study, we describe luciferase reporter mouse, which allows tracking gene induction vivo. Using reveal strong tissue-specific following infection influenza or La...
Background Several facultative anaerobic bacteria with potential therapeutic abilities are known to preferentially colonize solid tumors after systemic administration. How they efficiently find and invade the is still unclear. However, this an important issue be clarified when should tailored for application in cancer therapy. Methodology/Principal Findings We describe initial events of colonization ectopic transplantable tumor by Salmonella enterica serovar Typhimurium. Initially,...
To date, the mRNA delivery field has been heavily dominated by lipid-based systems. Reports on use of nonlipid carriers for in contrast are rare context vaccination. This paper describes potential a cell-penetrating peptide containing amphipathic RALA motif to deliver antigen-encoding immune system. condenses into nanocomplexes that display acidic pH-dependent membrane disruptive properties. enable escape from endosomes and thereby allow expression inside dendritic cell cytosol. Strikingly,...
Background Toll-like receptors (TLRs) are among the first-line sentinels for immune detection and responsiveness to pathogens. The TLR2 subfamily of TLRs (TLR1, TLR2, TLR6) form heterodimers with each other thus able recognize a broad range components from several microbes such as yeast, Gram-positive bacteria protozoa. Until now, activation by bacterial ligands has long been associated pro-inflammatory cytokines but not type I interferon responses. Methodology/Principal Findings Using...
Aicardi-Goutie `res syndrome (AGS), a hereditary autoimmune disease, clinically and biochemically overlaps with systemic lupus erythematosus (SLE) and, like SLE, is characterized by spontaneous type I interferon (IFN) production.The finding that defects of intracellular nucleases cause AGS led to the concept accumulation nucleic acids triggers inappropriate production IFN autoimmunity.AGS can also be caused SAMHD1, 3 0 exonuclease deoxynucleotide (dNTP) triphosphohydrolase.Human SAMHD1 an...
Abstract Localized therapeutic modalities that subvert the tumor microenvironment from immune‐suppressive to pro‐immunogenic can elicit systemic antitumor immune responses induce regression of directly treated as well nontreated distal tumors. A key toward generating robust T cell is activation dendritic cells (DCs) in microenvironment. Treatment with agonists triggering various pattern recognition receptors very efficient activate DCs, yet suffers induction serious immune‐related adverse...
Metastases are the major cause of death from cancer. Thus, understanding regulation metastatic processes is utmost importance. Here we show that mice with impaired type I IFN signaling (Ifnar1(-/-)) develop more lung metastases in 4T1 mammary and LLC carcinoma model, compared to control mice. In Ifnar1(-/-) mice, higher metastasis load accompanied by massive neutrophil accumulation lungs. Elevated G-CSF levels serum enhanced CXCR2 expression on neutrophils most likely responsible for this...
BackgroundInfection may trigger clinically overt mucosal inflammation in patients with predisposition for inflammatory bowel disease. However, the impact of particular enteropathogenic microorganisms is ill-defined. In this study, influence murine norovirus (MNV) infection on clinical, histopathological, and immunological features IL10-deficient (Il10−/−) mouse model disease was examined.
Activation of the RIG-I or STING pathways results in a type I interferon response that protects gut integrity after irradiation- immune-induced tissue injury.
In vitro transcribed mRNA constitutes a versatile platform to encode antigens and evoke CD8 T-cell responses. Systemic delivery of packaged into cationic liposomes (lipoplexes) has proven particularly powerful in achieving effective antitumor immunity animal models. Yet, responses lipoplexes critically depend on the induction type I interferons (IFN), potent pro-inflammatory cytokines, which inflict dose-limiting toxicities. Here, we explored an advanced hybrid lipid polymer shell...
γδ T cells are highly conserved in jawed vertebrates, suggesting an essential role the immune system. However, cell-deficient Tcrd-/- mice display surprisingly mild phenotypes. We hypothesized that lack of constitutive is functionally compensated by other lymphocytes taking over genuine cell functions. To test this, we generated a knock-in model for diphtheria toxin-mediated conditional depletion. In contrast to IFN-γ-producing cells, IL-17-producing (Tγδ17 cells) recovered inefficiently...
Given their high potential to evoke cytolytic T cell responses, tumor antigen-encoding messenger RNA (mRNA) vaccines are now being intensively explored as therapeutic cancer vaccines. mRNA clearly benefit from wrapping the into nano-sized carriers such lipoplexes that protect degradation and increase its uptake by dendritic cells in vivo. Nevertheless, early innate host factors regulate induction of lipoplex have remained unresolved. Here, we demonstrate induce a potent type I interferon...
Synthetic immune-stimulatory drugs such as agonists of the Toll-like receptors (TLR) 7/8 are potent activators antigen-presenting cells (APCs), however, they also induce severe side effects due to leakage from site injection into systemic circulation. Here, we report on design and synthesis an amphiphilic polymer-prodrug conjugate imidazoquinoline TLR7/8 agonist that in aqueous medium forms vesicular structures 200 nm. The contains endosomal enzyme-responsive linker enabling degradation...
Abstract The search for vaccines that protect from severe morbidity and mortality because of infection with acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), the virus causes disease 2019 (COVID‐19) is a race against clock virus. Here we describe an amphiphilic imidazoquinoline (IMDQ‐PEG‐CHOL) TLR7/8 adjuvant, consisting conjugated to chain end cholesterol‐poly(ethylene glycol) macromolecular amphiphile. It water‐soluble exhibits massive translocation lymph nodes upon local...