A5000384925- Immune Response and Inflammation
- Neuroinflammation and Neurodegeneration Mechanisms
- Immune cells in cancer
- Mosquito-borne diseases and control
- Bacterial Infections and Vaccines
- Viral Infections and Outbreaks Research
- Child Nutrition and Water Access
- Immunotherapy and Immune Responses
- Complement system in diseases
- Neuroscience and Neuropharmacology Research
- Multiple Sclerosis Research Studies
- Antimicrobial Peptides and Activities
- Congenital gastrointestinal and neural anomalies
- Extracellular vesicles in disease
- Caveolin-1 and cellular processes
- Virology and Viral Diseases
- Epilepsy research and treatment
- Image Processing Techniques and Applications
- Liver physiology and pathology
- Chronic Lymphocytic Leukemia Research
- HIV Research and Treatment
- Tryptophan and brain disorders
- Alzheimer's disease research and treatments
- Parasites and Host Interactions
- Coordination Chemistry and Organometallics
Washington University in St. Louis
2019-2024
Max Planck Institute of Experimental Medicine
2017-2020
Nanoscale Microscopy and Molecular Physiology of the Brain Cluster of Excellence 171 — DFG Research Center 103
2017-2019
Deutsche Forschungsgemeinschaft
2019
Universitätsmedizin Göttingen
2012-2017
University of Göttingen
2015
Czech Academy of Sciences, Institute of Microbiology
2014
The colonic epithelium can undergo multiple rounds of damage and repair, often in response to excessive inflammation. responsive stem cell that mediates this process is unclear, part because a lack vitro models recapitulate key epithelial changes occur vivo during repair. Here, we identify Hopx+ colitis-associated regenerative (CARSC) population functionally contributes mucosal repair mouse colitis. CARSCs, enriched for fetal-like markers, transiently arose from hypertrophic crypts known...
The underlying cellular mechanisms of catatonia, an executive "psychomotor" syndrome that is observed across neuropsychiatric diseases, have remained obscure. In humans and mice, reduced expression the structural myelin protein CNP associated with catatonic signs in age-dependent manner, pointing to involvement myelin-producing oligodendrocytes. Here, we showed cause low-grade inflammation white matter tracts, which marks a final common pathway Cnp-deficient other mutant mice minor...
Abstract Members of the low-density lipoprotein receptor (LDLR) family, including LDLRAD3, VLDLR, and ApoER2, were recently described as entry factors for different alphaviruses. However, based on studies with gene edited cells knockout mice, blockade or abrogation these receptors does not fully inhibit alphavirus infection, indicating existence additional uncharacterized factors. Here, we perform a CRISPR-Cas9 genome-wide loss-of-function screen in mouse neuronal chimeric expressing Eastern...
Microglia, innate immune cells of the CNS, sense infection and damage through overlapping receptor sets. Toll‐like (TLR) 4 recognizes bacterial lipopolysaccharide (LPS) multiple injury‐associated factors. We show that its co‐receptor CD14 serves three non‐redundant functions in microglia. First, it confers an up to 100‐fold higher LPS sensitivity compared peripheral macrophages enable efficient proinflammatory cytokine induction. Second, prevents excessive responses massive challenges via...
Prophylaxis with unmethylated cytosine phosphate guanidine (CpG) oligodeoxynucleotides (ODN) protects against several systemic experimental infections. Escherichia coli is a major cause of Gram-negative neonatal bacterial meningitis and also causes meningoencephalitis in older immunocompromised patients.Wild-type (wt) Toll-like receptor 9 (TLR9)-deficient mice were rendered neutropenic by intraperitoneal administration the anti-Ly-6G monoclonal antibody. Immunocompetent received CpG ODN or...
Abstract The determinants of severe disease caused by West Nile virus (WNV) and why only ~1% individuals progress to encephalitis remain poorly understood. Here, we use human mouse enteroids, a model pathogenesis, explore the capacity WNV directly infect gastrointestinal (GI) tract cells contribute severity. At baseline, infects enteroid cultures enterocytes in mice. However, when STAT1 or type I interferon (IFN) responses are absent, GI become infected, this is associated with augmented...
The putative protein tyrosine kinase (PTK) inhibitor tyrphostin AG126 has proven beneficial in various models of inflammatory disease. Yet molecular targets and cellular mechanisms remained enigmatic. We demonstrate here that treatment effects experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis. alleviates the clinical symptoms, diminishes encephalitogenic Th17 differentiation, reduces CNS infiltration as well microglia activation attenuates myelin damage. show...
Abstract Human mesial temporal lobe epilepsy (MTLE) features subregion‐specific hippocampal neurodegeneration and reactive astrogliosis, including up‐regulation of the glial fibrillary acidic protein (GFAP) down‐regulation glutamine synthetase (GS). However, regional astrocytic expression pattern GFAP GS upon MTLE‐associated still remains elusive. We assessed in strict correlation with local neuronal number cortical surgical specimens from 16 MTLE patients using immunohistochemistry,...
A growing body of evidence indicates that microglia actively remove synapses in vivo, thereby playing a key role synaptic refinement and modulation brain connectivity. This phenomenon was mainly investigated immunofluorescence staining confocal microscopy. However, quantification material using these techniques is extremely time-consuming labor-intensive. To address this issue, we aimed to quantify proteins flow cytometry. With approach, first showed from the healthy adult mouse contain...
Intestinal dysmotility syndromes have been epidemiologically associated with several antecedent bacterial and viral infections. To model this phenotype, we previously infected mice the neurotropic flavivirus West Nile virus (WNV) demonstrated intestinal transit defects. Here, found that within 1 week of WNV infection, enteric neurons glia became damaged, resulting in sustained reductions neuronal cells their networks connecting fibers. Using cell-depleting antibodies, adoptive transfer...
Adenylate cyclase toxin (CyaA) is a key virulence factor of the whooping cough agent Bordetella pertussis. The targets CD11b-expressing phagocytes and delivers into their cytosol an adenylyl (AC) enzyme that subverts cellular signaling by increasing cAMP levels. In present study, we analyzed modulatory effects CyaA on adhesive, migratory antigen presenting properties Toll-like receptor (TLR)-activated murine human dendritic cells (DCs). enhanced TLR-induced dissolution cell adhesive contacts...
Microglia as principle innate immune cells of the central nervous system (CNS) are first line defense against invading pathogens. They capable sensing infections through diverse receptors, such Toll-like receptor 4 (TLR4). This is best known for its ability to recognize bacterial lipopolysaccharide (LPS), a causative agent gram-negative sepsis and septic shock. A putative, naturally occurring antagonist TLR4 derives from photosynthetic bacterium Rhodobacter sphaeroides. However, antagonistic...
Reduced expression of 2′-3′-cyclic nucleotide 3′-phosphodiesterase (Cnp) in humans and mice causes white matter inflammation catatonic signs. These consequences are experimentally alleviated by microglia ablation via colony-stimulating factor 1 receptor (CSF1R) inhibition using PLX5622. Here we address for the first time preclinical topics crucial translation, most importantly 1) comparison 2 long-term PLX5622 applications (prevention treatment) vs. treatment alone, 2) correlation signs...
Venezuelan equine encephalitis virus (VEEV) is an encephalitic alphavirus responsible for epidemics of neurological disease across the Americas. Low-density lipoprotein receptor class A domain-containing 3 (LDLRAD3) a recently reported entry VEEV. Here, using wild-type and Ldlrad3-deficient mice, we define critical role LDLRAD3 in controlling steps VEEV infection, pathogenesis, neurotropism. Our analysis shows that required efficient infection pathogenesis prior to after central nervous...
Abstract Alphaviruses are enveloped positive-stranded RNA viruses of the Togaviridae family. Venezuelan equine encephalitis virus (VEEV) is an encephalitic alphavirus responsible for epidemics in and human populations across Americas. Its potential use as aerosolized bioterrorism weapon demonstrated risk it poses research settings highlight need countermeasures. VEEV pathogenesis characterized by a systemic inflammatory response central nervous system (CNS) infection, which can result severe...