A5011792550- Inflammasome and immune disorders
- Immune Cell Function and Interaction
- Neuropeptides and Animal Physiology
- IL-33, ST2, and ILC Pathways
- Immune Response and Inflammation
- interferon and immune responses
- Escherichia coli research studies
- Gut microbiota and health
- Cytokine Signaling Pathways and Interactions
- Helicobacter pylori-related gastroenterology studies
- Antimicrobial Peptides and Activities
- Eosinophilic Esophagitis
- Receptor Mechanisms and Signaling
- Clostridium difficile and Clostridium perfringens research
- T-cell and B-cell Immunology
- Peptidase Inhibition and Analysis
- Heme Oxygenase-1 and Carbon Monoxide
- Viral gastroenteritis research and epidemiology
- Inflammatory Bowel Disease
- Listeria monocytogenes in Food Safety
- Amoebic Infections and Treatments
- Immunotherapy and Immune Responses
- Neuroinflammation and Neurodegeneration Mechanisms
- Endoplasmic Reticulum Stress and Disease
- Biochemical and Structural Characterization
Oregon Health & Science University
2019-2025
University of California, Berkeley
2015-2021
Howard Hughes Medical Institute
2019
Paracelsus Medical University
2007-2018
Max Perutz Labs
2011-2015
University of Vienna
2011-2015
Unfallkrankenhaus Salzburg
2006-2008
Salzburger Landeskliniken
2007
Significance Measuring activity patterns of microbes in their natural environment is essential for understanding ecosystems and the multifaceted interactions microorganisms with eukaryotes. In this study, we developed a technique that allows fast nondestructive measurements microbial communities on single-cell level. Microbial were amended heavy water (D 2 O), treatment does not change available substrate pool. After incubation, physiologically active cells are rapidly identified Raman...
The animal and human intestinal mucosa secretes an assortment of compounds to establish a physical barrier between the host tissue contents, separation that is vital for health. Some pathogenic microorganisms as well members commensal microbiota have been shown be able break down these secreted compounds. Our understanding host-compound degradation by has limited knowledge about simplified model systems because difficulty in studying complex ecosystem vivo. In this study, we introduce...
Abstract Although alterations in gut microbiota composition during acute colitis have been repeatedly observed, associated functional changes and the recovery from dysbiosis received little attention. In this study, we investigated structure function of inflammation a dextran sodium sulfate (DSS)-colitis mouse model using metatranscriptomics, bacterial 16S rRNA gene amplicon sequencing monitoring selected host markers. Parallel to an increase markers colitis, observed relative abundance...
Acute colitis causes alterations in the intestinal microbiota, but microbiota is thought to recover after such events. Extreme are characteristic of human chronic inflammatory bowel diseases, although reported different studies divergent and sometimes even contradictory. To better understand impact periodic disturbances on its compositional difference between acute relapsing colitis, we investigated beginnings recurrent inflammation using dextran sodium sulfate (DSS) mouse model chemically...
NLRs (nucleotide-binding domain [NBD] leucine-rich repeat [LRR]–containing proteins) exhibit diverse functions in innate and adaptive immunity. NAIPs (NLR family, apoptosis inhibitory are that appear to function as cytosolic immunoreceptors for specific bacterial proteins, including flagellin the inner rod needle proteins of type III secretion systems (T3SSs). Despite strong biochemical evidence implicating detection ligands, genetic has been lacking. Here we report use CRISPR/Cas9 generate...
We investigated the role of inflammasome effector caspases-1 and -11 during Salmonella enterica serovar Typhimurium infection murine intestinal epithelial cells (IECs). burdens were significantly greater in intestines caspase-1/11 deficient (Casp1/11−/−), Casp1−/− Casp11−/− mice, as compared to wildtype mice. To determine if this reflected IEC-intrinsic inflammasomes, enteroid monolayers derived infected with Salmonella. responded similarly, whereas Casp1/11−/− carried increased...
Inflammasomes are cytosolic multi-protein complexes that detect infection or cellular damage and activate the Caspase-1 (CASP1) protease. The NAIP5/NLRC4 inflammasome detects bacterial flagellin is essential for resistance to flagellated intracellular bacterium Legionella pneumophila. effectors required downstream of restrict replication remain unclear. Upon activation, CASP1 cleaves activates pore-forming protein Gasdermin-D (GSDMD) effector caspase-7 (CASP7). However, Casp1–/– (and...
Bacteria of the genus Shigella cause shigellosis, a severe gastrointestinal disease that is major diarrhea-associated mortality in humans. Mice are highly resistant to and lack tractable physiological model shigellosis has impeded our understanding this important human disease. Here, we propose differential susceptibility mice humans due mouse-specific activation NAIP–NLRC4 inflammasome. We find NAIP–NLRC4-deficient susceptible oral infection recapitulate clinical features shigellosis....
Salmonella enterica serovar Typhimurium is a Gram-negative pathogen that uses two distinct type III secretion systems (T3SSs), termed pathogenicity island (SPI)-1 and SPI-2, to deliver virulence factors into the host cell. The SPI-1 T3SS enables invade cells, while SPI-2 facilitates Salmonella's intracellular survival. In mice, family of cytosolic immune sensors, including NAIP1, NAIP2, NAIP5/6, recognizes needle, inner rod, flagellin proteins, respectively. Ligand recognition triggers...
Salmonella enterica serovar Typhimurium is a Gram-negative pathogen that causes diseases ranging from gastroenteritis to systemic infection and sepsis. uses type III secretion systems (T3SS) inject effectors into host cells. While these are necessary for bacterial invasion intracellular survival, delivery of T3SS products also enables detection translocated ligands by cytosolic immune sensors. Some sensors form multimeric complexes called inflammasomes, which activate caspases lead...
The NAIP/NLRC4 inflammasome is a cytosolic sensor of bacteria that activates caspase-1 and initiates potent immune responses. Structural, biochemical, genetic data demonstrate NAIP proteins are receptors for bacterial ligands, while NLRC4 downstream adaptor multimerizes with NAIPs to form an inflammasome. has also been proposed suppress tumor growth, though the underlying mechanism unknown. Further, phosphorylated on serine 533, which was suggested be critical its function. In absence S533...
Type 2 inflammation is associated with epithelial cell responses, including goblet hyperplasia, that promote worm expulsion during intestinal helminth infection. How these responses are regulated remains incompletely understood. Here, we show mice deficient in the prostaglandin D2 (PGD2) receptor CRTH2 and deficiency only nonhematopoietic cells exhibited enhanced clearance hyperplasia following infection Nippostrongylus brasiliensis. Small stem, goblet, tuft expressed CRTH2. CRTH2-deficient...
Transcriptional activation of the Nos2 gene, encoding inducible nitric oxide synthase (iNOS), during infection or inflammation requires coordinate assembly an initiation complex by transcription factors NF-B and type I interferon-activated ISGF3.Here we show that macrophages with intracellular bacterial pathogen Listeria monocytogenes caused binding BET proteins Brd2, Brd3, and, most prominently, Brd4 to promoter a profound reduction expression occurred in presence inhibitor JQ1.RNA...
The interferon (IFN)-stimulated gene factor 3 (ISGF3) transcription with its Stat1, Stat2, and regulatory 9 (IRF9) subunits is employed for transcriptional responses downstream of receptors type I interferons (IFN-I) that include IFN-α IFN-β III (IFN-III), also called IFN-λ. Here, we show in a murine model dextran sodium sulfate (DSS)-induced colitis IRF9 deficiency protects animals, whereas the combined loss IFN-I IFN-III worsens their condition. We explain different phenotypes by...
ABSTRACT The commensal Streptococcus sanguinis is highly prevalent in the oral cavity and characterized for its ability to inhibit growth of pathogens. Like many other cell types, streptococci produce extracellular membrane vesicles (EMVs), which contain specific molecular cargo facilitate interactions with host cells. We previously demonstrated that EMVs from S. are internalized by gingival epithelial cells (GECs) without causing death. Our aim characterize effects on eukaryotic Microscopy...
To distinguish pathogens from commensals, the intestinal epithelium employs cytosolic innate immune sensors. Activation of NAIP–NLRC4 inflammasome initiates extrusion infected epithelial cells (IEC) upon bacterial sensing. We previously reported that activation in tuft cells, which are primarily known for their role parasitic infections, leads to release prostaglandin D2 (PGD2). observe an antibacterial response with increased IL-22 and antimicrobial protein levels within small intestine, is...
Galanin-like peptide (GALP) is a hypothalamic neuropeptide belonging to the galanin family of peptides. The GALP gene characterized by extensive differential splicing in variety murine tissues. One splice variant excludes exon 3 and results frame shift leading novel sequence stop codon after 49 aa. In this peptide, which we termed alarin, signal precursor first 5 aa mature are followed 20 without homology any other protein. Alarin mRNA was detected brain, thymus, skin. accordance with its...
The contribution of the innate immune system to inflammatory bowel disease (IBD) is under intensive investigation. Research in animal models has demonstrated that type I interferons (IFN-Is) protect from IBD. In contrast, studies patients with IBD have produced conflicting results concerning therapeutic potential IFN-Is. Here, we present data suggesting IFN-Is play dual roles as regulators intestinal inflammation dextran sodium sulfate (DSS)-treated C57BL/6 mice. Though reduced acute damage...
In the intestinal tract, IL-22 activates STAT3 to promote epithelial cell (IEC) homeostasis and tissue healing. The mechanism has remained obscure, but we demonstrate that acts via tyrosine kinase 2 (Tyk2), a member of Jak family. Using mouse model for colitis, show Tyk2 deficiency is associated with an altered composition gut microbiota exacerbates inflammatory bowel disease. Colitic Tyk2(-/-) mice have less p-STAT3 in colon their IECs proliferate efficiently. Tyk2-deficient primary reduced...
Listeria monocytogenes is a food-borne pathogen which causes mild to life threatening disease in humans. Ingestion of contaminated food delivers the gastrointestinal tract, where it crosses epithelial barrier and spreads internal organs. Type I interferons (IFN-I) are produced during infection decrease host resistance after systemic delivery L. monocytogenes. Here we show that mice benefit from IFN-I production following with via route. Intragastric lead increased lethality receptor chain...