scholarly journals Mast cell deficiency in mice results in biomass overgrowth and delayed expulsion of the rat tapeworm Hymenolepis diminuta

2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Marisol I. González ◽  
Fernando Lopes ◽  
Derek M. McKay ◽  
José L. Reyes
Keyword(s):  
Cellular Response ◽  
In Vitro Release ◽  
Hymenolepis Diminuta ◽  
Mouse Strains ◽  
Helminth Parasites ◽  
Th2 Response ◽  
Helminthic Infections ◽  
Worm Expulsion ◽  
Deficient Mice

Infection with helminth parasites evokes a complex cellular response in the host, where granulocytes (i.e. eosinophils, basophils and mast cells (MCs)) feature prominently. In addition to being used as markers of helminthic infections, MCs have been implicated in worm expulsion since animals defective in c-kit signaling, which results in diminished MC numbers, can have delayed worm expulsion. The role of MCs in the rejection of the rat tapeworm, Hymenolepsis diminuta, from the non-permissive mouse host is not known. MC-deficient mice display a delay in the expulsion of H. diminuta that is accompanied by a less intense splenic Th2 response, as determined by in vitro release of interleukin (IL)-4, IL-5 and IL-13 cytokines. Moreover, worms retrieved from MC-deficient mice were larger than those from wild-type (WT) mice. Assessment of gut-derived IL-25, IL-33, thymic stromal lymphopoietin revealed lower levels in uninfected MC-deficient mice compared with WT, suggesting a role for MCs in homeostatic control of these cytokines: differences in these gut cytokines between the mouse strains were not observed after infection with H. diminuta. Finally, mice infected with H. diminuta display less severe dinitrobenzene sulphonic acid (DNBS)-induced colitis, and this beneficial effect of the worm was unaltered in MC-deficient mice challenged with DNBS, as assessed by a macroscopic disease score. Thus, while MCs are not essential for rejection of H. diminuta from mice, their absence slows the kinetics of expulsion allowing the development of greater worm biomass prior to successful rejection of the parasitic burden.

scholarly journals Studies on the anthelmintic potentials of the roots of Asparagus racemosus willd. (Asparagaceae)

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Amar Deep Soren ◽  
Arun Kumar Yadav
Keyword(s):  
Hymenolepis Diminuta ◽  
Comparable Efficacy ◽  
Asparagus Racemosus ◽  
Helminth Parasites ◽  
Reference Drug ◽  
Nematode Parasites ◽  
Helminthic Infections ◽  
Syphacia Obvelata

Abstract Background The Santhal tribe in Assam, India use the roots of Asparagus racemosus (Asparagaceae) as a deworming remedy. The study aimed to investigate the anthelmintic credentials of this plant, using two representative groups of helminth parasites. Methods The in vitro testing was conducted against Hymenolepis diminuta (cestode) and Syphacia obvelata (nematode). Parasites were exposed to 10, 20 and 30 mg/ml concentrations of plant extract, and efficacy was adjudged on the basis of parasites paralysis and mortality. In vivo efficacy was examined using H. diminuta-rat and S. obvelata-mice models where animals were administered 125, 250 and 500 mg/kg doses of extract. Results In vitro assay, against H. diminuta revealed that at 30 mg/ml concentration the extract showed almost a comparable efficacy with that of reference drug praziquantel (PZQ) (1 mg/ml). The in vitro efficacy of extract against S. obvelata was however lower than H. diminuta. In vivo studies against H. diminuta at 500 mg/kg revealed 53.88 and 24 % reduction in eggs per gram (EPG) and worm counts respectively. Against S. obvelata the extract showed 26.61 and 30.93 % reduction for the same. Conclusions The findings of this study present suggest that the roots of A. racemosus are effective against intestinal helminthic infections and justifies its use as an anthelmintic in the traditional medicine of the Santhals.

scholarly journals The state of art of neutrophil extracellular traps in protozoan and helminthic infections

2019 ◽  
Vol 39 (1) ◽  
Author(s):  
César Díaz-Godínez ◽  
Julio C. Carrero
Keyword(s):  
Neutrophil Extracellular Traps ◽  
Parasitic Infections ◽  
Parasitic Diseases ◽  
Helminth Parasites ◽  
Extracellular Traps ◽  
Helminthic Infections ◽  
Bacteria And Fungi ◽  
Net Release

AbstractNeutrophil extracellular traps (NETs) are DNA fibers associated with histones, enzymes from neutrophil granules and anti-microbial peptides. NETs are released in a process denominated NETosis, which involves sequential steps that culminate with the DNA extrusion. NETosis has been described as a new mechanism of innate immunity related to defense against different pathogens. The initial studies of NETs were carried out with bacteria and fungi, but currently a large variety of microorganisms capable of inducing NETs have been described including protozoan and helminth parasites. Nevertheless, we have little knowledge about how NETosis process is carried out in response to the parasites, and about its implication in the resolution of this kind of disease. In the best case, the NETs entrap and kill parasites in vitro, but in others, immobilize the parasites without affecting their viability. Moreover, insufficient studies on the NETs in animal models of infections that would help to define their role, and the association of NETs with chronic inflammatory pathologies such as those occurring in several parasitic infections have left open the possibility of NETs contributing to pathology instead of protection. In this review, we focus on the reported mechanisms that lead to NET release by protozoan and helminth parasites and the evidence that support the role of NETosis in the resolution or pathogenesis of parasitic diseases.

scholarly journals Alum adjuvant boosts adaptive immunity by inducing uric acid and activating inflammatory dendritic cells

2008 ◽  
Vol 205 (4) ◽  
pp. 869-882 ◽  
Author(s):  
Mirjam Kool ◽  
Thomas Soullié ◽  
Menno van Nimwegen ◽  
Monique A.M. Willart ◽  
Femke Muskens ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Uric Acid ◽  
Lymph Node ◽  
Danger Signal ◽  
Th2 Response ◽  
Inflammatory Monocytes ◽  
Cellular And Humoral Immunity ◽  
Inflammatory Dendritic Cells ◽  
Deficient Mice

Alum (aluminum hydroxide) is the most widely used adjuvant in human vaccines, but the mechanism of its adjuvanticity remains unknown. In vitro studies showed no stimulatory effects on dendritic cells (DCs). In the absence of adjuvant, Ag was taken up by lymph node (LN)–resident DCs that acquired soluble Ag via afferent lymphatics, whereas after injection of alum, Ag was taken up, processed, and presented by inflammatory monocytes that migrated from the peritoneum, thus becoming inflammatory DCs that induced a persistent Th2 response. The enhancing effects of alum on both cellular and humoral immunity were completely abolished when CD11c+ monocytes and DCs were conditionally depleted during immunization. Mechanistically, DC-driven responses were abolished in MyD88-deficient mice and after uricase treatment, implying the induction of uric acid. These findings suggest that alum adjuvant is immunogenic by exploiting “nature's adjuvant,” the inflammatory DC through induction of the endogenous danger signal uric acid.

scholarly journals A264 HELMINTH-INFECTION MOBILIZES HOST AND MICROBIAL FACTORS THAT CO-OPERATE TO SUPPRESS CHEMICAL-INDUCED COLITIS IN MICE

2020 ◽  
Vol 3 (Supplement_1) ◽  
pp. 141-142
Author(s):  
A J Shute ◽  
B E Callejas Pina ◽  
T S Jayme ◽  
A Wang ◽  
A Buret ◽  
...  
Keyword(s):  
Drinking Water ◽  
Murine Model ◽  
Hymenolepis Diminuta ◽  
Model Systems ◽  
Epithelial Cell Line ◽  
Helminth Parasites ◽  
Critical Determinant ◽  
The Individual ◽  
Helminth Therapy

Abstract Background Infection with helminth parasites suppresses inflammation in murine model systems; for example, IL-10 is important in Hymenolepis diminuta-inhibition of DNBS-induced colitis. Bacteria-derived products can have anti-inflammatory effects. Given that infection with H. diminuta, or other parasitic worms, results in perturbation of the gut microbiota, the present study tested a role for bacteria in helminth-suppression of colitis by assessing reciprocity between IL-10 and butyrate signaling in the amelioration of colitis. Aims To determine if a functional relationship exists between IL-10 and butyrate in the inhibition of colitis observed following infection with the lumen-dwelling tapeworm, Hymenolepis diminuta. Methods Colitis was induced in male BALB/c mice by intra-rectal dinitrobenzene sulphonic acid (DNBS) (3 mg/~22g mouse), with necropsy and assessment 3 days later. Mice received either infection with five H. diminuta cysticercoids by gavage or daily butyrate enemas or acetate in their drinking water. Immunostaining assessed IL-10R protein expression on formalin-fixed sections of colon. The murine IEC4.1 epithelial cell line and epithelial organoids were treated with butyrate and mRNA for the IL10Rα chain assessed, as was colonic tissue from mice. Results Mice infected with H. diminuta or receiving butyrate enemas (n=8–12) were protected from DNBS-induced colitis as gauged by colon length, and macroscopic disease and histopathology scores. Addition of acetate to the drinking water resulted in a more modest anti-colitic effect. Suppression of colitis was accompanied by increased epithelial expression of IL-10 in butyrate- and H. diminuta-treated mice, with the later also showing upregulation of the IL-10R on lamina propria cells; an effect negated by co-treating the mice with broad spectrum antibiotics. In vitro analyses revealed increased IL10Rα mRNA in butyrate-treated epithelia (n=4). Conclusions This study begins to tease apart the host (i.e. IL-10) and bacterial (i.e. butyrate) molecules that mediate H. diminuta-evoked suppression of colitis in a murine model. These proof-of-principle data suggest that knowledge of the individual patient (i.e. immunological basis of their disease and their microbiota) may be a critical determinant of the success or failure of helminth therapy. Funding Agencies CAG, CCCNSERC

scholarly journals The skin is an important bulwark of acquired immunity against intestinal helminths

2013 ◽  
Vol 210 (12) ◽  
pp. 2583-2595 ◽  
Author(s):  
Kazushige Obata-Ninomiya ◽  
Kenji Ishiwata ◽  
Hidemitsu Tsutsui ◽  
Yuichiro Nei ◽  
Soichiro Yoshikawa ◽  
...  
Keyword(s):  
Lung Injury ◽  
Intestinal Helminth ◽  
Nippostrongylus Brasiliensis ◽  
Arginase 1 ◽  
Helminthic Infections ◽  
Selective Ablation ◽  
Helminthic Infection ◽  
Worm Expulsion ◽  
Deficient Mice ◽  
Infected Skin

Once animals have experienced a helminthic infection, they often show stronger protective immunity against subsequent infections. Although helminthic infections are well known to elicit Th2-type immune responses, it remains ill-defined where and how acquired protection is executed. Here we show that skin-invading larvae of the intestinal helminth Nippostrongylus brasiliensis are surrounded by skin-infiltrating cells and are prevented from migrating out of infected skin during the second but not the first infection. B cell– or IgE receptor FcεRI–deficient mice showed impaired larval trapping in the skin. Selective ablation of basophils, but not mast cells, abolished the larval trapping, leading to increased worm burden in the lung and hence severe lung injury. Skin-infiltrating basophils produced IL-4 that in turn promoted the generation of M2-type macrophages, leading to the larval trapping in the skin through arginase-1 production. Basophils had no apparent contribution to worm expulsion from the intestine. This study thus reveals a novel mode of acquired antihelminth immunity, in which IgE-armed basophils mediate skin trapping of larvae, thereby limiting lung injury caused by larval migration.

scholarly journals Role of Complement Receptors in Uptake ofMycobacterium avium by Macrophages In Vivo: Evidence from Studies Using CD18-Deficient Mice

1999 ◽  
Vol 67 (9) ◽  
pp. 4912-4916 ◽  
Author(s):  
Luiz E. Bermudez ◽  
Joseph Goodman ◽  
Mary Petrofsky
Keyword(s):  
Mouse Strains ◽  
Histopathological Study ◽  
Intracellular Pathogen ◽  
Complement Receptors ◽  
Transmission Electron ◽  
Granulomatous Lesions ◽  
Deficient Mice

ABSTRACT Mycobacterium avium is an intracellular pathogen that has been shown to invade macrophages by using complement receptors in vitro, but mycobacteria released from one cell can enter a second macrophage by using receptors different from complement receptors. Infection of CD18 (β2 integrin) knockout mice and the C57 BL/6 control mice led to comparable levels of tissue infection at 1 day, 2 days, 1 week, and 3 weeks following administration of bacteria. A histopathological study revealed similar granulomatous lesions in the two mouse strains, with comparable numbers of organisms. In addition, transmission electron microscopy of spleen tissues from both strains of mice showed bacteria inside macrophages. Our in vivo findings support the hypothesis that M. avium in the host is likely to use receptors other than CR3 and CR4 receptors to enter macrophages with increased efficiency.

scholarly journals Impaired c-Jun Amino Terminal Kinase Activity and T Cell Differentiation in Death Receptor 6–deficient Mice

2001 ◽  
Vol 194 (10) ◽  
pp. 1441-1448 ◽  
Author(s):  
Haoran Zhao ◽  
Minhong Yan ◽  
Hua Wang ◽  
Sharon Erickson ◽  
Iqbal S. Grewal ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Differentiation ◽  
Death Receptor ◽  
Death Domain ◽  
Th2 Response ◽  
Apoptotic Pathway ◽  
Th Cells ◽  
Amino Terminal ◽  
Deficient Mice

During an immune response naive T helper (Th) cells differentiate into two functionally distinct subsets, Th1 and Th2, based on their cytokine secretion profile and immunomodulatory function. c-Jun amino terminal kinase (JNK) regulates Th cell differentiation by activating a transcriptional program required for cytokine production. We have recently identified a TNFR superfamily death domain–containing molecule, death receptor (DR)6, which potently activates JNK. T cells from DR6-deficient mice are substantially impaired in JNK activation. When DR6−/− mice were challenged with protein antigen, their T cells hyperproliferate and display a profound polarization toward a Th2 response whereas Th1 differentiation is not equivalently affected. In addition, DR6−/− T cells showed preference toward Th2 differentiation in vitro. The phenotype seen in the DR6−/− mice is not due to the apoptotic pathway. Therefore, DR6, working through JNK, rather than apoptosis, functions to attenuate the Th2 response. This is the first demonstration of a role in the activation and differentiation of Th cells by DR6 in particular and DRs in general.

scholarly journals A Trypsin-Sensitive Proteoglycan from the Tapeworm Hymenolepis diminuta Inhibits Murine Neutrophil Chemotaxis in vitro by Suppressing p38 MAP Kinase Activation

2018 ◽  
Vol 11 (2) ◽  
pp. 136-149 ◽  
Author(s):  
Nicholas Graves ◽  
Vivek P. Venu ◽  
Bryan G. Yipp ◽  
Björn Petri ◽  
Simon Hirota ◽  
...  
Keyword(s):  
Interleukin 10 ◽  
Leukotriene B4 ◽  
P38 Map Kinase ◽  
Hymenolepis Diminuta ◽  
Mitogen Activated Protein Kinase ◽  
Helminth Parasites ◽  
Neutrophil Chemotaxis ◽  
Sodium Metaperiodate ◽  
Inflammatory Conditions

It has emerged that neutrophils can play important roles in the host response following infection with helminth parasites. Mice infected with the tapeworm, Hymenolepis diminuta, are protected from some inflammatory conditions, accompanied by reduced neutrophil tissue infiltration. Thus, the ability of a phosphate-buffered saline-soluble extract of the worm (H. diminuta extract [HdE]) was tested for (1) its ability to activate murine neutrophils (Ca2+ mobilization, reactive oxygen species (ROS) and cytokine production); and (2) affect neutrophil chemotaxis in vitro to the penta-peptide, WKYMVm, the chemokine, KC, and leukotriene B4. HdE was not cytotoxic to neutrophils, elicited a Ca2+ response and ROS, but not, cytokine (KC, interleukin-10, tumour necrosis factor-α) generation. HdE is not a chemotactic stimulus for murine neutrophils. However, a heat- and trypsin-sensitive, acid-insensitive proteoglycan (sensitive to sodium metaperiodate) in the HdE significantly reduced neutrophil chemotaxis towards WKYMVm or KC, but not LTB4. The latter suggested that the HdE interfered with p38 mitogen-activated protein kinase signalling, which is important in WKYMVm chemotaxis. Corroborating this, immunoblotting revealed reduced phosphorylated p38, and the downstream signal heat-shock protein-27, in protein extracts from HdE + WkYMVm treated cells compared to those exposed to the penta-peptide only. We speculate that HdE can be used to modify the outcome of neutrophilic disease and that purification of the bioactive proteoglycan(s) from the extract could be used as a template to design immunomodulatory drugs targeting neutrophils.

Study on in vitro release patterns of fentanyl-loaded PLGA microspheres

2003 ◽  
Vol 20 (5) ◽  
pp. 569-579 ◽  
Author(s):  
S.-A. Seo ◽  
G. Khang ◽  
J. M. Rhee ◽  
J. Kim ◽  
H. B. Lee
Keyword(s):  
In Vitro Release ◽  
Plga Microspheres ◽  
Vitro Release

Minimal contribution of cell-bound antibodies to the immunoscintigraphy of inflamed joints with 99mTc-anti-CD4 monoclonal antibodies

2002 ◽  
Vol 41 (03) ◽  
pp. 129-134 ◽  
Author(s):  
A. Wolski ◽  
E. Palombo-Kinne ◽  
F. Wolf ◽  
F. Emmrich ◽  
W. Becker ◽  
...  
Keyword(s):  
T Cells ◽  
Monoclonal Antibodies ◽  
Synovial Membrane ◽  
In Vitro Release ◽  
Peritoneal Macrophages ◽  
Lymphoid Organs ◽  
Whole Body ◽  
Free Form ◽  
Ankle Joints

Summary Aim: The cellular joint infiltrate in rheumatoid arthritis patients is rich in CD4-positive T-helper lymphocytes and macrophages, rendering anti-CD4 monoclonal antibodies (mAbs) suitable for specific immunoscintigraphy of human/ experimental arthritis. Following intravenous injection, however, mAbs are present both in the free form and bound to CD4-positive, circulating monocytes and T-cells. Thus, the present study aimed at analyzing the relative contribution of the free and the cell-bound component to the imaging of inflamed joints in experimental adjuvant arthritis (AA). Methods: AA rat peritoneal macrophages or lymph node T-cells were incubated in vitro with saturating amounts of 99mTc-anti-CD4 mAb (W3/25) and injected i.v. into rats with AA. Results: In vitro release of 99mTc-anti-CD4 mAb from the cells was limited (on average 1.57%/h for macrophages and 0.84%/h for T-cells). Following i.v. injection, whole body/joint scans and tissue measurements showed only negligible accumulation of radioactivity in inflamed ankle joints (tissue: 0.22 and 0.34% of the injected activity, respectively), whereas the radioactivity was concentrated in liver (tissue: 79% and 71%, respectively), kidney, and urinary bladder. Unlike macrophages, however, anti-CD4 mAb-coated T-cells significantly accumulated in lymphoid organs, the inflamed synovial membrane of the ankle joints, as well as in elbow and knee joints. Conclusion: While the overall contribution of cell-bound mAbs to the imaging of arthritic joints with anti-CD4 mAbs is minimal, differential accumulation of macrophages and T-cells in lymphoid organs and the inflamed synovial membrane indicates preferential migration patterns of these 2 cell populations in arthritic rats. Although only validated for 99mTc-anti-CD4 mAbs, extrapolation of the results to other anticellular mAbs with similar affinity for their antigen may be possible.

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