Mitochondrial swelling induced by diphtheria toxin in vivo: A comparison with the action of some other bacterial toxins

1967 ◽  
Vol 23 (12) ◽  
pp. 1045-1047 ◽  
Author(s):  
F. Paradisi
Keyword(s):  
Diphtheria Toxin ◽  
Bacterial Toxins ◽  
Mitochondrial Swelling

scholarly journals Inducible ablation of mouse Langerhans cells diminishes but fails to abrogate contact hypersensitivity

2005 ◽  
Vol 169 (4) ◽  
pp. 569-576 ◽  
Author(s):  
Clare L. Bennett ◽  
Erwin van Rijn ◽  
Steffen Jung ◽  
Kayo Inaba ◽  
Ralph M. Steinman ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Steady State ◽  
Diphtheria Toxin ◽  
Langerhans Cells ◽  
Contact Hypersensitivity ◽  
Relative Importance ◽  
Skin Immunity

Langerhans cells (LC) form a unique subset of dendritic cells (DC) in the epidermis but so far their in vivo functions in skin immunity and tolerance could not be determined, in particular in relation to dermal DC (dDC). Here, we exploit a novel diphtheria toxin (DT) receptor (DTR)/DT-based system to achieve inducible ablation of LC without affecting the skin environment. Within 24 h after intra-peritoneal injection of DT into Langerin-DTR mice LC are completely depleted from the epidermis and only begin to return 4 wk later. LC deletion occurs by apoptosis in the absence of inflammation and, in particular, the dDC compartment is not affected. In LC-depleted mice contact hypersensitivity (CHS) responses are significantly decreased, although ear swelling still occurs indicating that dDC can mediate CHS when necessary. Our results establish Langerin-DTR mice as a unique tool to study LC function in the steady state and to explore their relative importance compared with dDC in orchestrating skin immunity and tolerance.

scholarly journals Altered ratio of dendritic cell subsets in skin-draining lymph nodes promotes Th2-driven contact hypersensitivity

2021 ◽  
Vol 118 (3) ◽  
pp. e2021364118
Author(s):  
Hannah L. Miller ◽  
Prabhakar Sairam Andhey ◽  
Melissa K. Swiecki ◽  
Bruce A. Rosa ◽  
Konstantin Zaitsev ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Lymph Nodes ◽  
Diphtheria Toxin ◽  
Fluorescein Isothiocyanate ◽  
Skin Inflammation ◽  
Contact Hypersensitivity ◽  
Type I ◽  
Th2 Response ◽  
Draining Lymph Nodes

Plasmacytoid dendritic cells (pDCs) specialize in the production of type I IFN (IFN-I). pDCs can be depleted in vivo by injecting diphtheria toxin (DT) in a mouse in which pDCs express a diphtheria toxin receptor (DTR) transgene driven by the human CLEC4C promoter. This promoter is enriched for binding sites for TCF4, a transcription factor that promotes pDC differentiation and expression of pDC markers, including CLEC4C. Here, we found that injection of DT in CLEC4C-DTR+ mice markedly augmented Th2-dependent skin inflammation in a model of contact hypersensitivity (CHS) induced by the hapten fluorescein isothiocyanate. Unexpectedly, this biased Th2 response was independent of reduced IFN-I accompanying pDC depletion. In fact, DT treatment altered the representation of conventional dendritic cells (cDCs) in the skin-draining lymph nodes during the sensitization phase of CHS; there were fewer Th1-priming CD326+ CD103+ cDC1 and more Th2-priming CD11b+ cDC2. Single-cell RNA-sequencing of CLEC4C-DTR+ cDCs revealed that CD326+ DCs, like pDCs, expressed DTR and were depleted together with pDCs by DT treatment. Since CD326+ DCs did not express Tcf4, DTR expression might be driven by yet-undefined transcription factors activating the CLEC4C promoter. These results demonstrate that altered DC representation in the skin-draining lymph nodes during sensitization to allergens can cause Th2-driven CHS.

Protective Effects on Mitochondria and Anti-Aging Activity of Polysaccharides from Cultivated Fruiting Bodies of Cordyceps militaris

2010 ◽  
Vol 38 (06) ◽  
pp. 1093-1106 ◽  
Author(s):  
Xing-Tai Li ◽  
Hong-Cheng Li ◽  
Chun-Bin Li ◽  
De-Qiang Dou ◽  
Ming-Bo Gao
Keyword(s):  
Hydroxyl Radicals ◽  
Cordyceps Militaris ◽  
Mitochondrial Swelling ◽  
Dependent Manner ◽  
Protective Effects ◽  
Fruiting Bodies ◽  
Concentration Dependent Manner ◽  
Mitochondrial Injury

Cordyceps militaris (L.) Link is an entomopathogenic fungus parasitic to Lepidoptera larvae, and is widely used as a folk tonic or invigorant for longevity in China. Although C. militaris has been used in traditional Chinese medicine for millennia, there is still a lack convincing evidence for its anti-aging activities. This study was performed to investigate the effects of polysaccharides from cultivated fruiting bodies of C. militaris (CMP) on mitochondrial injury, antioxidation and anti-aging activity. Fruiting bodies of C. militaris were cultivated artificially under optimized conditions. The spectrophotometric method was used to measure thiobarbituric acid reactive substances (TBARS), mitochondrial swelling, and activities of scavenging superoxide anions in vitro. D-galactose (100 mg/kg/day) was injected subcutaneously into back of the neck of mice for 7 weeks to induce an aging model. The effects of CMP on the activities of catalase (CAT), surperoxide dismutase (SOD), glutathione peroxidase (GPx) and anti-hydroxyl radicals were assayed in vivo using commercial monitoring kits. The results showed that CMP could inhibit mitochondrial injury and swelling induced by Fe2+ -L-Cysteine in a concentration- dependent manner and it also had a significant superoxide anion scavenging effect. Moreover, the activities of CAT, SOD, GPx and anti-hydroxyl radicals in mice liver were increased significantly by CMP. These results indicate that CMP protects mitochondria by scavenging reactive oxygen species (ROS), inhibiting mitochondrial swelling, and increasing the activities of antioxidases. Therefore, CMP may have pharmaceutical values for mitochondrial protection and anti-aging. CMP was the major bioactive component in C. militaris.

scholarly journals Interleukin 2-diphtheria toxin fusion protein can abolish cell-mediated immunity in vivo.

1988 ◽  
Vol 85 (11) ◽  
pp. 3980-3984 ◽  
Author(s):  
V. E. Kelley ◽  
P. Bacha ◽  
O. Pankewycz ◽  
J. C. Nichols ◽  
J. R. Murphy ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Diphtheria Toxin ◽  
Interleukin 2 ◽  
Cell Mediated Immunity

scholarly journals Recent advances with Treg depleting fusion protein toxins for cancer immunotherapy

Immunotherapy ◽  
2019 ◽  
Vol 11 (13) ◽  
pp. 1117-1128 ◽  
Author(s):  
Pankaj Kumar ◽  
Amit Kumar ◽  
Sadiya Parveen ◽  
John R Murphy ◽  
William Bishai
Keyword(s):  
Diphtheria Toxin ◽  
Antitumor Immunity ◽  
T Regulatory Cells ◽  
Treg Cells ◽  
Clinical Development ◽  
Bacterial Toxins ◽  
Regulatory Cells ◽  
Protein Toxins ◽  
Cancer Immunotherapies ◽  
Pseudomonas Aeruginosa Exotoxin

T regulatory cells (Tregs) are an important T cell population for immune tolerance, prevention of autoimmune diseases and inhibition of antitumor immunity. The tumor-promoting role played by Tregs in cancer has prompted numerous approaches to develop immunotherapeutics targeting Tregs. One approach to depletion of Treg cells is retargeting the highly potent cytotoxic activity of bacterial toxins. These agents capitalize on the well-characterized bacterial toxins, diphtheria toxin and Pseudomonas aeruginosa exotoxin A–both of which harbor membrane translocation domains and enzymatic domains that catalytically halt protein synthesis within intoxicated eukaryotic cells and act at picomolar or subpicomolar concentrations. In this review, we summarize the preclinical and clinical development of several Treg-depleting cancer immunotherapies based on these two bacterial toxins.

scholarly journals Endosomal proteolysis of diphtheria toxin without toxin translocation into the cytosol of rat liver in vivo

FEBS Journal ◽  
2008 ◽  
Vol 275 (8) ◽  
pp. 1708-1722 ◽  
Author(s):  
Tatiana El Hage ◽  
Paulette Decottignies ◽  
François Authier
Keyword(s):  
Rat Liver ◽  
Diphtheria Toxin

scholarly journals INACTIVATION OF BACTERIAL EXOTOXINS AND ENDOTOXIN BY IRON

1960 ◽  
Vol 112 (1) ◽  
pp. 23-34 ◽  
Author(s):  
Aaron Janoff ◽  
Benjamin W. Zweifach
Keyword(s):  
Guinea Pigs ◽  
Diphtheria Toxin ◽  
Reticuloendothelial System ◽  
Partial Recovery ◽  
Alpha Toxin ◽  
Lethal Effects ◽  
Partial Restoration ◽  
Manganese Zinc

After incubation with various agents in vitro, the lethal effects of aqueous solutions of Cl. perfringens alpha toxin, C. diphtheriae toxin, and E. coli endotoxin were tested in mice, guinea pigs, and rabbits, respectively. Iron, copper, cysteine, ascorbic acid, and versene counteracted the lethal effects of alpha toxin in mice, while magnesium, manganese, zinc, and citrate did not. Iron also counteracted the lethal effects of diphtheria toxin in guinea pigs. After incubation of endotoxin with iron, its lethal effects and tissue-necrotizing actions in rabbits were counteracted. However, the pyrogenic properties of the toxin were not affected. The solubilities of perfringens alpha toxin and diphtheria toxin were markedly reduced after incubation with detoxifying metals, and resolubilization of these toxins with chelators resulted in partial restoration of toxicity. Addition of versene to detoxified endotoxin also resulted in partial recovery of lethal effectiveness. The inactivation of bacterial toxins by iron under in vitro conditions is not specific to this metal, is a reversible process, and may be due to desolubilization, reduction, or to competition by the metal for sites on the toxin normally bound by other cations in vivo. Although no evidence is presented in this paper to support the view that there is a relationship between the inactivation of endotoxin and the storage iron in the reticuloendothelial system of shocked animals, the observation of an in vitro inactivation of endotoxin by inorganic iron warrants consideration of such a mechanism.

scholarly journals Diphtheria-toxin based anti-human CCR4 immunotoxin for targeting human CCR4+ cells in vivo

2015 ◽  
Vol 9 (7) ◽  
pp. 1458-1470 ◽  
Author(s):  
Zhaohui Wang ◽  
Min Wei ◽  
Huiping Zhang ◽  
Hongyuan Chen ◽  
Sharon Germana ◽  
...  
Keyword(s):  
Diphtheria Toxin
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