Search results for "Unity"
showing 10 items of 3852 documents
Adaptive suppression of the ATF4–CHOP branch of the unfolded protein response by toll-like receptor signalling
2009
The endoplasmic reticulum (ER) unfolded protein response (UPR) restores equilibrium to the ER, but prolonged expression of the UPR effector CHOP (GADD153) is cytotoxic. We found that CHOP expression induced by ER stress was suppressed by prior engagement of toll-like receptor (TLR) 3 or 4 through a TRIF-dependent pathway. TLR engagement did not suppress phosphorylation of PERK or eIF-2alpha, which are upstream of CHOP, but phospho-eIF-2alpha failed to promote translation of the CHOP activator ATF4. In mice subjected to systemic ER stress, pretreatment with low dose lipopolysaccharide (LPS), a TLR4 ligand, suppressed CHOP expression and apoptosis in splenic macrophages, renal tubule cells an…
Alkaline Phosphatase: Keeping the Peace at the Gut Epithelial Surface
2007
Vertebrates harbor abundant lipopolysaccharide (LPS) or endotoxin in their gut microbiota. Here we demonstrate that the brush border enzyme intestinal alkaline phosphatase (Iap), which dephosphorylates LPS, is induced during establishment of the microbiota and plays a crucial role in promoting mucosal tolerance to gut bacteria in zebrafish. We demonstrate that Iap deficient animals are hypersensitive to LPS toxicity through a mechanism mediated by Myd88 and Tumor Necrosis Factor Receptor (Tnfr). We further show that the endogenous microbiota establish the normal homeostatic level of neutrophils in the intestine through a process involving Myd88 and Tnfr. Iap deficient animals exhibit excess…
The Host Response toListeria monocytogenesMutants Defective in Genes Encoding Phospholipases C(plcA, plcB)and Actin Assembly(actA)
1997
Several genes involved in the determination of Listeria monocytogenes pathogenesis have been identified. Among them, plcA gene encodes phosphatidylinositol-specific phospholipase C (PI-PLC), plcB gene encodes a broad-range phospholipase C (PC-PLC), and actA encodes a protein contributing to actin assembly in infected cells. The interaction of L. monocytogenes wild type (LO 28) strain and two derivative mutants, plcA- (BUG 206) and actA-/plcB- (LUT 12), with macrophages and T lymphocytes was investigated in a mouse model of listeriosis. Both mutants showed evidence of attenuation. The plcA- mutant, but not the plcB- mutant, expressed an increase in susceptibility to the anti-listerial activi…
Phenolic-glycolipid-1 and lipoarabinomannan preferentially modulate TCR- and CD28-triggered proximal biochemical events, leading to T-cell unresponsi…
2012
Abstract Background Advanced stages of leprosy show T cell unresponsiveness and lipids of mycobacterial origin are speculated to modulate immune responses in these patients. Present study elucidates the role of phenolicglycolipid (PGL-1) and Mannose-capped lipoarabinomannan (Man-LAM) on TCR- and TCR/CD28- mediated signalling. Results We observed that lipid antigens significantly inhibit proximal early signalling events like Zap-70 phosphorylation and calcium mobilization. Interestingly, these antigens preferentially curtailed TCR-triggered early downstream signalling events like p38 phosphorylation whereas potentiated that of Erk1/2. Further, at later stages inhibition of NFAT binding, IL-2…
A member of the Tlr family is involved in dsRNA innate immune response in Paracentrotus lividus sea urchin
2015
Abstract The innate immune response involves proteins such as the membrane receptors of the Toll-like family (TLRs), which trigger different intracellular signalling pathways that are dependent on specific stimulating molecules. In sea urchins, TLR proteins are encoded by members of a large multigenic family composed of 60–250 genes in different species. Here, we report a newly identified mRNA sequence encoding a TLR protein (referred to as Pl-Tlr) isolated from Paracentrotus lividus immune cells. The partial protein sequence contained the conserved Toll/IL-1 receptor (TIR) domain, the transmembrane domain and part of the leucine repeats. Phylogenetic analysis of the Pl-Tlr protein was acco…
T cell proliferation in the mixed lymphocyte culture does not necessarily result in the generation of cytotoxic T effector cells.
1975
It was tested whether T lymphocytes, when stimulated in vitro by M locus-coded lymphocyte activating determinants (LAD), are able to mediate cytotoxic effector functions. The assay for cytotoxicity included both the use of purified appropriate target cells (i.e. purified lipopolysaccharide blasts) as well as the use of phytohemagglutinin dependent cytolysis as a model for detecting cytotoxic T lymphocytes (CTL). Although strong proliferative responses were obtained in the mixed lymphocyte culture, the T cell blast generated did not display any detectable cytotoxic effector function. Thus, it is concluded that LAD, at least in the M locus-dependenet system, do have the capacity to induce T c…
An experimental test of the dose-dependent effect of carotenoids and immune activation on sexual signals and antioxidant activity.
2004
Carotenoid‐based sexual traits are thought to be reliable indicators of male quality because they might be scarce and therefore might indicate the ability of males to gather high‐quality food and because they are involved in important physiological functions (as immune enhancers and antioxidants). We performed an experiment where male and female zebra finches (Taeniopygia guttata) were provided with increasing carotenoid doses in the drinking water during 4 weeks (bill color of this species is a carotenoid‐based sexual signal). Simultaneously, birds were split into two groups: one receiving weekly injections of Escherichia coli lipopolysaccharide in order to activate the immune system, the …
HSP60 and CpG-DNA-oligonucleotides differentially regulate LPS-tolerance of hepatic Kupffer cells
2004
Background/aims: Hepatic Kupffer cells (KC) are major regulators of the immune response to gut-derived bacterial products; uncontrolled activation of KC by bacterial components is of pathogenic relevance in alcoholic hepatitis and septic shock. Methods: We examined the role of bacterial lipopolysaccharide (LPS), bacterial and autologous HSP60 and bacterial DNA, which are recognized by innate Toll-like receptors, during activation of murine KC. Results: In cultivated KC, autologous HSP60 induced a state of LPS-hyporesponsiveness; bacterial DNA did not mitigate the response to subsequent LPS-challenge in vitro; in contrast, pre-treatment of mice with bacterial DNA even significantly increased…
Differential uptake and killing potential of Campylobacter jejuni by human peripheral monocytes/macrophages
1997
The ability of Campylobacter jejuni to survive in monocytes after phagocytic uptake was tested in a new in vitro model using adherent macrophages derived from human peripheral monocytes. The cells were stimulated with cytokines before use to ensure full phagocytic and killing activity. The kinetics of uptake and killing of bacteria was followed for 72 h with 16 strains, including stool and blood isolates and laboratory adapted strains. Significant bacterial strain differences were not observed, but the viability of phagocytosed bacteria was dependent on the individual donating the macrophages. The majority of blood donors carried macrophages that killed phagocytosed Campylobacter within 24 …
Ciona intestinalis peroxinectin is a novel component of the peroxidase–cyclooxygenase gene superfamily upregulated by LPS
2013
Peroxinectins function as hemoperoxidase and cell adhesion factor involved in invertebrate immune reaction. In this study, the ascidian (Ciona intestinalis) peroxinectin gene (CiPxt) and its expression during the inflammatory response have been examined. CiPxt is a new member of the peroxidase-cyclooxygenase gene superfamily that contains both the peroxidase domain and the integrin KGD (Lys-Gly-Asp) binding motif. A phylogenetic tree showed that CiPxt is very close to the chordate group and appears to be the outgroup of mammalian MPO, EPO and TPO clades. The CiPxt molecular structure model resulted superimposable to the human myeloperoxidase. The CiPxt mRNA expression is upregulated by LPS …