A5075858306- Inflammasome and immune disorders
- interferon and immune responses
- Cell death mechanisms and regulation
- Phagocytosis and Immune Regulation
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Immune Response and Inflammation
- Salmonella and Campylobacter epidemiology
- Vibrio bacteria research studies
- Escherichia coli research studies
- Streptococcal Infections and Treatments
- Heme Oxygenase-1 and Carbon Monoxide
- Burkholderia infections and melioidosis
- IL-33, ST2, and ILC Pathways
- Viral Infections and Vectors
- Kawasaki Disease and Coronary Complications
- Autoimmune and Inflammatory Disorders Research
- Microbial Metabolism and Applications
- Bacteriophages and microbial interactions
- Yersinia bacterium, plague, ectoparasites research
- Endoplasmic Reticulum Stress and Disease
- Immune responses and vaccinations
- Immune Cell Function and Interaction
- Erythrocyte Function and Pathophysiology
- Gout, Hyperuricemia, Uric Acid
- RNA regulation and disease
Duke University
2020-2025
Piedmont International University
2025
University of North Carolina at Chapel Hill
2014-2024
National Institutes of Health
2024
Bipar
2015
Institute for Systems Biology
2006-2011
Center for Infectious Disease Research
2011
Seattle University
2006-2010
University of Washington
1999-2006
Czech Academy of Sciences, Institute of Microbiology
1999
Move Over, TLR4 The innate immune system senses bacterial lipopolysaccharide (LPS) through Toll-like receptor 4 (TLR4) (see the Perspective by Kagan ). However, Kayagaki et al. (p 1246 , published online 25 July) and Hagar (p. 1250 ) report that hexa-acyl lipid A component of LPS from Gramnegative bacteria is able to access cytoplasm activate caspase-11 signal responses independently TLR4. Mice lack are resistant LPS-induced lethality, even in presence
The mammalian innate immune system uses Toll-like receptors (TLRs) and Nod-LRRs (NLRs) to detect microbial components during infection. Often these molecules work in concert; for example, the TLRs can stimulate production of proforms cytokines IL-1beta IL-18, whereas certain NLRs trigger their subsequent proteolytic processing via caspase 1. Gram-negative bacteria use type III secretion systems (T3SS) deliver virulence factors cytosol host cells, where they modulate cell physiology favor...
Caspases are either apoptotic or inflammatory. Among inflammatory caspases, caspase-1 and -11 trigger pyroptosis, a form of programmed cell death. Whereas both can be detrimental in disease, only has an established protective role during infection. Here, we report that caspase-11 is required for innate immunity to cytosolic, but not vacuolar, bacteria. Although Salmonella typhimurium Legionella pneumophila normally reside the vacuole, specific mutants (sifA sdhA, respectively) aberrantly...
Acute lung injury is a leading cause of death in bacterial sepsis due to the wholesale destruction endothelial barrier, which results protein-rich edema, influx proinflammatory leukocytes, and intractable hypoxemia. Pyroptosis form programmed lytic cell that triggered by inflammatory caspases, but little known about its role EC acute injury. Here, we show systemic exposure endotoxin lipopolysaccharide (LPS) causes severe pyroptosis mediated human caspases 4/5 ECs, or murine homolog...
Inflammasomes activate caspase-1 in response to cytosolic contamination or perturbation. This inflammatory caspase triggers the opening of GSDMD pore plasma membrane, resulting lytic cell death called pyroptosis. We had previously assumed that pyroptosis releases intracellular bacteria extracellular space. Here, we find viable instead remain trapped within cellular debris pyroptotic macrophages. trapping appears be an inevitable consequence how osmotic lysis ruptures and may also apply...
IFN receptor signaling induces cell-autonomous immunity to infections with intracellular bacterial pathogens. Here, we demonstrate that IFN-inducible guanylate binding protein (Gbp) proteins stimulate caspase-11-dependent, in response cytoplasmic LPS. Caspase-11-dependent pyroptosis is triggered IFN-activated macrophages infected the Gram-negative pathogen Legionella pneumophila. The rapid induction of required a cluster Gbp encoded on mouse chromosome 3 (Gbp(chr3)). Induction naive by...
The innate immune system encodes cytosolic Nod-like receptors (NLRs), several of which activate caspase 1 processing and IL-1beta IL-18 secretion. Macrophages respond to Salmonella typhimurium infection by activating through the NLR Ipaf. This activation is mediated flagellin activity virulence-associated type III secretion (T3SS). We demonstrate here that Pseudomonas aeruginosa activates induces in infected macrophages. While live, virulent P. Ipaf, strains have mutations T3SS or did not....
Type III secretion systems (TTSS) are important virulence factors that Gram-negative bacteria use to translocate proteins into the cytoplasm of eukaryotic host cells. Salmonellae encode two virulence-associated TTSS. The Salmonella pathogenicity island 1 (SPI1)-encoded TTSS is active on contact with cells, whereas 2 (SPI2)-encoded expressed after phagocytosis by Previously, no consensus signal sequence for translocation has been identified among effector proteins. In this work, seven...
Salmonellae encode two virulence‐associated type III secretion systems (TTSS) within Salmonella pathogenicity islands 1 and 2 (SPI1 SPI2). Two typhimurium genes, sspH1 sspH2 , that proteins similar to the Shigella flexneri Yersinia species TTSS substrates, IpaH YopM, were identified. SspH1 SspH2 are containing leucine‐rich repeats differentially targeted SPI1 SPI2 TTSS. transcription was induced RAW264.7 macrophages, dependent upon SPI2‐encoded regulator ssrA/ssrB . In contrast, is...
ABSTRACT The genetic basis for the host adaptation of Salmonella serotypes is currently unknown. We have explored a new strategy to identify enterica serotype Typhimurium ( S. typhimurium ) genes involved in adaptation, by comparing virulence 260 randomly generated signature-tagged mutants during oral infection mice and calves. This screen identified four mutants, which were defective colonization only one two species tested. One mutant, displayed defect mice, was further characterized....
Characterization of an animal model may explain why not all patients with multiple sclerosis respond to interferon-β.