A5051811775- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- interferon and immune responses
- T-cell and B-cell Immunology
- Monoclonal and Polyclonal Antibodies Research
- Immune Response and Inflammation
- Herpesvirus Infections and Treatments
- Cytokine Signaling Pathways and Interactions
- SARS-CoV-2 and COVID-19 Research
- Viral Infections and Vectors
- Allergic Rhinitis and Sensitization
- Wnt/β-catenin signaling in development and cancer
- Asthma and respiratory diseases
- Hemophilia Treatment and Research
- Poxvirus research and outbreaks
- Food Allergy and Anaphylaxis Research
- Cytomegalovirus and herpesvirus research
- Biosimilars and Bioanalytical Methods
- Virus-based gene therapy research
- Glycosylation and Glycoproteins Research
- Influenza Virus Research Studies
- Viral gastroenteritis research and epidemiology
- Respiratory viral infections research
- Complement system in diseases
- Muscle Physiology and Disorders
Paul Ehrlich Institut
2015-2024
Novel (Germany)
2010-2017
German Center for Infection Research
2015
Response Biomedical (Canada)
2009
Harvard University
2006
Medizinische Hochschule Hannover
2006
Goethe University Frankfurt
2000-2002
Activation of the cannabinoid 2 receptor (CB2) reduces ischemic injury in several organs. However, mechanisms underlying this protective action are unclear. In a mouse model stroke, we show that CB2 agonist JWH-133 (1 mg • kg"1 d"1) decreases infarct size measured 3 d after onset ischemia. The neuroprotective effect was lost CB2-deficient mice, confirming specificity JWH-133. Analysis bone marrow chimeric mice revealed marrow-derived cells mediate on brain injury. activation reduced number...
ABSTRACT In 2012, the first cases of infection with Middle East respiratory syndrome coronavirus (MERS-CoV) were identified. Since then, more than 1,000 MERS-CoV have been confirmed; is typically associated considerable morbidity and, in approximately 30% cases, mortality. Currently, there no protective vaccine available. Replication-competent recombinant measles virus (MV) expressing foreign antigens constitutes a promising tool to induce immunity against corresponding pathogens. Therefore,...
The Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012 as the causative agent of a severe disease with fatality rate approximately 30%. high virulence and mortality prompted us to analyze aspects MERS-CoV pathogenesis, especially its interaction innate immune cells such antigen-presenting (APCs). Particularly, we analyzed secretion type I III interferons (IFNs) by APCs, i.e., B cells, macrophages, monocyte-derived/myeloid dendritic (MDDCs/mDCs), plasmacytoid (pDCs) human...
The exact role of innate immune cells upon infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and their contribution to the formation corona virus-induced disease (COVID)-19 associated cytokine storm is not yet fully understood. We show that human in vitro differentiated myeloid dendritic (mDC) as well M1 M2 macrophages are susceptible SARS-CoV-2 but productively infected. Furthermore, infected mDC, M1-, only slight changes activation status. Surprisingly, none...
Vaccine-associated enhanced respiratory disease (VAERD) is a severe complication for some infections. To investigate the potential VAERD induction in coronavirus 2019 (COVID-19), we evaluate two vaccine leads utilizing hamster infection model: T helper type 1 (TH1)-biased measles vaccine-derived candidate and TH2-biased alum-adjuvanted, non-stabilized spike protein. The virus (MeV)-derived protects animals, but protein lead induces VAERD, which can be alleviated by dexamethasone treatment....
FHL2 is a LIM-domain protein expressed in myoblasts but down-regulated malignant rhabdomyosarcoma cells, suggesting an important role of muscle development. To investigate the importance during myoblast differentiation, we performed yeast two-hybrid screen using cDNA library derived from induced for differentiation. We identified β-catenin as novel interaction partner and confirmed specificity association by direct vitro binding tests coimmunoprecipitation assays cell lysates. Deletion...
ABSTRACT Modified vaccinia virus Ankara (MVA) is a highly attenuated strain undergoing clinical evaluation as replication-deficient vaccine vector against various infections and tumor diseases. To analyze the basis of its high immunogenicity, we investigated mechanism how MVA induces type I interferon (IFN) responses. stimulation bone marrow-derived dendritic cells (DC) showed that plasmacytoid DC were main alpha IFN (IFN-α) producers triggered independently productive infection, viral...
Production of type I interferons (IFN-I, mainly IFNα and IFNβ) is a hallmark innate immune responses to all classes pathogens. When viral infection spreads lymphoid organs, the majority systemic IFN-I produced by specialized “interferon-producing cell” (IPC) that has been shown belong lineage plasmacytoid dendritic cells (pDC). It unclear whether production generally attributable pDC irrespective nature infecting pathogen. We have addressed this question studying infections mice with...
Superagonistic CD28 antibodies (CD28SAs) activate T lymphocytes without concomitant perturbation of the TCR/CD3-complex. In rodents these reagents induce preferential expansion regulatory cells and can be used for treatment autoimmune diseases. Unexpectedly, humanized superagonist TGN1412 caused severe life threatening adverse effects during a recently conducted phase I clinical trail. The underlying molecular mechanisms are as yet unclear. We show that well commercially available ANC28.1...
Poxviruses such as virulent vaccinia virus (VACV) strain Western Reserve encode a broad range of immune modulators that interfere with host responses to infection. Upon more than 570 in vitro passages chicken embryo fibroblasts (CEF), chorioallantois VACV Ankara (CVA) accumulated mutations resulted highly attenuated modified (MVA). MVA infection mice and dendritic cells (DC) induced significant type I interferon (IFN) responses, whereas alone or combination did not. These results implied...
This work focuses on the need for modeling and predicting adverse outcomes in immunotoxicology to improve nonclinical assessments of safety immunomodulatory therapies. The integrated approach includes, first, outcome pathway concept established toxicology field, and, second, systems medicine disease map describing molecular mechanisms involved a particular pathology. proposed workflow is illustrated with chimeric antigen receptor (CAR) T cell treatment as use case. To this end, linear (AOP)...
Activation of the latent kinase PKR is a potent innate defense reaction vertebrate cells towards viral infections, which triggered by recognition double-stranded (ds) RNA and results in translational shutdown. A major gap our understanding PKR's antiviral properties concerns nature activating molecules expressed influenza other viruses with negative strand genome, as these pathogens produce little or no detectable amounts dsRNA. Here we systematically investigated activation B virus its...
Interfering with interferon: A low-molecular-weight inhibitor has been discovered that blocks the interaction between interferon-α (IFN-α) and its receptor (see picture for a model of interfaces). The resulting lead compound significantly reduces IFN-α production in vitro. NMR SPR experiments confirm direct IFN-α.
Therapeutic monoclonal antibodies (mAbs) such as the superagonistic, CD28-specific antibody TGN1412, or OKT3, an anti-CD3 mAb, can cause severe adverse events including cytokine release syndrome. A predictive model for mAb-mediated effects, which no previous knowledge on to be expected molecular mechanisms underlying is prerequisite, not available yet. We used a humanized mouse of human peripheral blood mononuclear cell-reconstituted NOD-RAG1-/-Aβ-/-HLADQ(tg+ tg-)IL-2Rγc-/- mice evaluate its...
The delivery of protein fragments to major histocompatibility complex (MHC)-loading compartments professional antigen-presenting cells is essential in the adaptive immune response against pathogens. Apart from crucial role transporter associated with antigen processing (TAP) for peptide loading MHC class I molecules endoplasmic reticulum, TAP-independent translocation pathways have been proposed but not identified so far. Based on its overlapping substrate specificity TAP, we herein...
Abstract Upon stimulation with a wide range of concentrations CpG oligodeoxynucleotide 2216 (CpG 2216), plasmacytoid DC are induced to produce type I IFN (IFN‐α/β). In contrast, 1668 shows bell‐shaped dose–response correlation, i.e. only intermediate but not high doses induce IFN‐α/β. Interestingly, high‐dose completely inhibited IFN‐α responses by 2216. Experiments using supernatant CpG‐1668‐treated cells indicated that secreted inhibitor(s) mediated the shut‐off. Among modulating...