scholarly journals Exosomes secreted by nematode parasites transfer small RNAs to mammalian cells and modulate innate immunity

2014 ◽  
Vol 5 (1) ◽  
Author(s):  
Amy H. Buck ◽  
Gillian Coakley ◽  
Fabio Simbari ◽  
Henry J. McSorley ◽  
Juan F. Quintana ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Gastrointestinal Nematode ◽  
Parasitic Nematodes ◽  
Heligmosomoides Polygyrus ◽  
Nematode Parasites ◽  
Intestinal Origin ◽  
Mouse Cells ◽  
Host Tissues

Abstract In mammalian systems RNA can move between cells via vesicles. Here we demonstrate that the gastrointestinal nematode Heligmosomoides polygyrus, which infects mice, secretes vesicles containing microRNAs (miRNAs) and Y RNAs as well as a nematode Argonaute protein. These vesicles are of intestinal origin and are enriched for homologues of mammalian exosome proteins. Administration of the nematode exosomes to mice suppresses Type 2 innate responses and eosinophilia induced by the allergen Alternaria. Microarray analysis of mouse cells incubated with nematode exosomes in vitro identifies Il33r and Dusp1 as suppressed genes, and Dusp1 can be repressed by nematode miRNAs based on a reporter assay. We further identify miRNAs from the filarial nematode Litomosoides sigmodontis in the serum of infected mice, suggesting that miRNA secretion into host tissues is conserved among parasitic nematodes. These results reveal exosomes as another mechanism by which helminths manipulate their hosts and provide a mechanistic framework for RNA transfer between animal species.

scholarly journals Some larval morphological characteristics of Camelostrongylus mentulatus and Nematodirus spathiger

2020 ◽  
Vol 3 (2) ◽  
pp. 7-11
Author(s):  
A. Saidi ◽  
R. Mimouni ◽  
F. Hamadi ◽  
W. Oubrou
Keyword(s):  
Morphological Characteristics ◽  
Gastrointestinal Nematode ◽  
Parasitic Nematodes ◽  
Morphological Identification ◽  
Morphological Pattern ◽  
Wild Ruminants ◽  
Nematode Parasites ◽  
Domestic Ruminants ◽  
Teladorsagia Circumcincta ◽  
Camelostrongylus Mentulatus

Monitoring of gastrointestinal nematode parasites in ruminants (domestic and wild) is often based on fecal examination techniques, looking for excreted eggs and larval forms using morphological keys. These, are more available in domestic ruminants, in which helminths are widely studied, than in wild ruminants.  This study tried to provide certain morphological elements that will help to recognize the L3 larvae of Camelostrongylus mentulatus and Nematodirus spathiger that could parasite either domestic or wild ruminants. For that, we resorted first to the culture of L3 larvae from fecal samples taken from African antelopes, and second by the microscopic characterization of each isolated larval morphological pattern previously identified by sequencing of its internal transcribed spacer (ITS-2) regions of the ribosomal DNA. The results of different microscopic captured images showed that Camelostrongylus mentulatus larva is 16 intestinal cells that measuring approximately 820 µm length, ‎≈ 25 µm wide, and ‎≈ 47 µm for its sheath tail extension and by this be closer to Teladorsagia circumcincta characteristics.  For Nematodirus spathiger, it possesses 8 gut cells and measuring about 1020 µm long, ‎≈ 25 µm wide, and‎ ≈ 143 µm for its sheath tail extension with specific tail appendages. Have done this, we were able to get some clarifications on the morphology of the studied larvae, and we believe thus that this study will contribute to the establishment of morphological identification keys especially for parasitic nematodes of wild ruminants.

scholarly journals In Vitro Efficacy of Aqueous and Methanol Extract of Cassia siamea Against the Motility of Caenorhabditis elegans

2020 ◽  
Vol 31 (3) ◽  
pp. 145-159
Author(s):  
Haladu Ali Gagman ◽  
Nik Ahmad Irwan Izzauddin Nik Him ◽  
Hamdan Ahmad ◽  
Shaida Fariza Sulaiman ◽  
Rahmad Zakaria ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Methanol Extract ◽  
Anthelmintic Resistance ◽  
Gastrointestinal Nematode ◽  
Parasitic Nematodes ◽  
Cassia Siamea ◽  
Methanol Extracts ◽  
C Elegans ◽  
Significant Difference

Gastrointestinal nematode infections can cause great losses in revenue due to decrease livestock production and animal death. The use of anthelmintic to control gastrointestinal nematode put a selection pressure on nematode populations which led to emergence of anthelmintic resistance. Because of that, this study was carried out to investigate the efficacy of aqueous and methanol extract of Cassia siamea against the motility of C. elegans Bristol N2 and C. elegans DA1316. Caenorhabditis elegans Bristol N2 is a susceptible strain and C. elegans DA1316 is an ivermectin resistant strain. In vitro bioassay of various concentrations of (0.2, 0.6, 0.8, 1.0 and 2.0 mg mL–1) aqueous and methanol extracts of C. siamea was conducted against the motility of L4 larvae of C. elegans Bristol N2 and C. elegans DA1316. The L4 larvae were treated with 0.02 μg mL–1 of ivermectin served as positive control while those in M9 solution served as negative control. The activity of the extracts was observed after 24 h and 48 h. A significant difference was recorded in the extract performance compared to control at (P < 0.001) after 48 h against the motility of the larvae of both strains. The methanol extracts inhibited the motility of C. elegans Bristol N2 by 86.7% as well as DA1316 up to 84.9% at 2.0 mg mL–1 after 48 h. The methanol extract was more efficient than aqueous extract (P < 0.05) against the motility of both strains of C. elegans. Cassia siamea may be used as a natural source of lead compounds for the development of alternative anthelmintic against parasitic nematodes as well ivermectin resistant strains of nematodes.

Correction of Genetic Defects in Mammalian Cells by the Input of Small Amounts of Foreign Genetic Material

1973 ◽  
Vol 13 (3) ◽  
pp. 841-861
Author(s):  
YVONNE L. BOYD ◽  
H. HARRIS
Keyword(s):  
Thymidine Kinase ◽  
Mammalian Cells ◽  
Hybrid Cell ◽  
Genetic Material ◽  
Chinese Hamster ◽  
Heat Sensitivity ◽  
Chinese Hamster Cells ◽  
Inosinic Acid ◽  
Mouse Cells

Chinese hamster cells lacking inosinic acid pyrophosphorylase and mouse cells lacking thymidine kinase were fused with chick erythrocytes. The resultant heterokaryons were cultivated in a selective medium in which possession of these enzymes was essential for cell survival and growth. Clones of cells able to grow in this medium were isolated and studied. A detailed karyological analysis of these clones failed to reveal any chick chromosomes; nor could any chick-specific antigens be detected on the surface of the cells. Nonetheless, clones arising from the fusion of chick erythrocytes with Chinese hamster cells were shown to possess an inosinic acid pyrophosphorylase which had the electrophoretic characteristics of chick inosinic acid pyrophosphorylase. However, the clones arising from the fusion of the chick erythrocytes with the mouse cells had a thymidine kinase with the electrophoretic mobility and heat sensitivity of murine, not chick, thymidine kinase. Both types of hybrid cell have now been cultivated in vitro for 18 months without the loss of thymidine kinase or inosinic acid pyrophosphorylase activity.

EFFECTS OF ANAEROBIOSIS ON THE RATES OF MULTIPLICATION OF MAMMALIAN CELLS CULTURED IN VITRO

1960 ◽  
Vol 38 (1) ◽  
pp. 871-878 ◽  
Author(s):  
Samuel Dales
Keyword(s):  
Mammalian Cells ◽  
Glucose Utilization ◽  
Lactic Acid Production ◽  
Cell Types ◽  
In Vitro Cultures ◽  
Cell Multiplication ◽  
Embryonic Mouse ◽  
Mouse Cells ◽  
Oxidation Of Glucose

To test the effects of anaerobiosis on the rate of multiplication and carbohydrate metabolism of mammalian cells in vitro, cultures of a 'permanent' line, Earle's L strain cells, and of freshly explanted embryonic mouse cells were propagated in the presence and absence of oxygen. Contrary to the findings of several other investigators, our results show that the multiplication of both cell types was depressed by anaerobiosis. Anaerobiosis for at least 7 days, did not, however, bring about unbalanced growth in L cells, nor did it affect their capability to divide rapidly soon after they were returned to aerobic conditions. From the rates of glucose utilization, lactic acid production, and cell multiplication it was estimated that the rate of division in the two cell types studied was proportional to the energy which could be released from either glycolysis or complete oxidation of glucose.

scholarly journals Assessment of the anthelmintic effect of natural plant cysteine proteinases against the gastrointestinal nematode, Heligmosomoides polygyrus, in vitro

Parasitology ◽  
2004 ◽  
Vol 130 (2) ◽  
pp. 203-211 ◽  
Author(s):  
G. STEPEK ◽  
D. J. BUTTLE ◽  
I. R. DUCE ◽  
A. LOWE ◽  
J. M. BEHNKE
Keyword(s):  
Mechanism Of Action ◽  
Cysteine Proteinase ◽  
Gastrointestinal Nematode ◽  
Cysteine Proteinase Inhibitor ◽  
Cysteine Proteinases ◽  
Fruit Extract ◽  
Potent Effect ◽  
Kiwi Fruit ◽  
Heligmosomoides Polygyrus

We examined the mechanism of action and compared the anthelmintic efficacy of cysteine proteinases from papaya, pineapple, fig, kiwi fruit and Egyptian milkweed in vitro using the rodent gastrointestinal nematode Heligmosomoides polygyrus. Within a 2 h incubation period, all the cysteine proteinases, with the exception of the kiwi fruit extract, caused marked damage to the cuticle of H. polygyrus adult male and female worms, reflected in the loss of surface cuticular layers. Efficacy was comparable for both sexes of worms, was dependent on the presence of cysteine and was completely inhibited by the cysteine proteinase inhibitor, E-64. LD50 values indicated that the purified proteinases were more efficacious than the proteinases in the crude latex, with purified ficin, papain, chymopapain, Egyptian milkweed latex extract and pineapple fruit extract, containing fruit bromelain, having the most potent effect. The mechanism of action of these plant enzymes (i.e. an attack on the protective cuticle of the worm) suggests that resistance would be slow to develop in the field. The efficacy and mode of action make plant cysteine proteinases potential candidates for a novel class of anthelmintics urgently required for the treatment of humans and domestic livestock.

scholarly journals Characterization of a Rhodanese Homologue from Haemonchus Contortus and its Immune-Modulatory Effects on Goat Immune Cells in Vitro

2020 ◽  
Author(s):  
Yujian Wang ◽  
Muhammad Ehsan ◽  
Jianmei Huang ◽  
Kalibixiati Aimulajiang ◽  
RuoFeng Yan ◽  
...  
Keyword(s):  
Haemonchus Contortus ◽  
Mononuclear Cells ◽  
Small Ruminants ◽  
Parasitic Nematodes ◽  
Dependent Manner ◽  
Peripheral Blood Mononuclear ◽  
Nematode Parasites ◽  
Wide Range

Abstract Background: Suppression and modulation of the immune response of the host by nematode parasites have been reported widely. Rhodaneses or thiosulfate: cyanide sulfurtransferases are present in a wide range of organisms, such as archea, bacteria, fungi, plants and animals. Previously, it was reported that a rhodanese homology could bind by goat peripheral blood mononuclear cells (PBMCs) in vivo.Results: In the present study, we cloned and produced recombinant rhodanese protein originated from Haemonchus contortus (rHCRD), which was one of the parasitic nematodes of small ruminants. The effect of this protein on modulating the immunity of goat PBMC and monocyte was studied in the current work. The predominant localization of the natural HCRD protein was verified as the bowel wall and body surface of worms, according to the immunohistochemical tests. It was proved in this study that the serum produced by artificially infecting goats with H. contortus successfully recognized rHCRD which conjugated goat PBMCs. The rHCRD was co-incubated with goat PBMCs to observe the immunomodulatory effect on proliferation, apoptosis and secretion of cytokines exerted by HCRD. The results showed that the interaction of rHCRD suppressed proliferation of goat PBMCs stimulated by ConA but did not induce the apoptosis of goat PBMCs. After rHCRD exposure, the production of TNF-α and IFN-γ were significantly decreased, however, it significantly increased the secretion of IL-10 and TGF-β1 in goat PBMCs. Phagocytotic assay by FITC-dextran internalization showed that rHCRD inhibited the phagocytosis of goat monocytes. Moreover, rHCRD could down-regulate the expression of MHC-II on goat monocytes in a dose-dependent manner. Conclusions: These discoveries proposed a possible target as immunomodulator, which was potentially beneficial to illuminate the interaction between parasites and hosts in the molecular level and hunt for innovative protein species as candidate targets of drug and vaccine.

scholarly journals A helminth-derived suppressor of ST2 blocks allergic responses

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Francesco Vacca ◽  
Caroline Chauché ◽  
Abhishek Jamwal ◽  
Elizabeth C Hinchy ◽  
Graham Heieis ◽  
...  
Keyword(s):  
Immune Responses ◽  
Heligmosomoides Polygyrus ◽  
Human Pbmc ◽  
Complement Control Protein ◽  
High Affinity ◽  
Intestinal Nematode ◽  
Control Protein

The IL-33-ST2 pathway is an important initiator of type 2 immune responses. We previously characterised the HpARI protein secreted by the model intestinal nematode Heligmosomoides polygyrus, which binds and blocks IL-33. Here, we identify H. polygyrus Binds Alarmin Receptor and Inhibits (HpBARI) and HpBARI_Hom2, both of which consist of complement control protein (CCP) domains, similarly to the immunomodulatory HpARI and Hp-TGM proteins. HpBARI binds murine ST2, inhibiting cell surface detection of ST2, preventing IL-33-ST2 interactions, and inhibiting IL-33 responses in vitro and in an in vivo mouse model of asthma. In H. polygyrus infection, ST2 detection is abrogated in the peritoneal cavity and lung, consistent with systemic effects of HpBARI. HpBARI_Hom2 also binds human ST2 with high affinity, and effectively blocks human PBMC responses to IL-33. Thus, we show that H. polygyrus blocks the IL-33 pathway via both HpARI which blocks the cytokine, and also HpBARI which blocks the receptor.

scholarly journals Adenosine metabolized from extracellular ATP promotes type 2 immunity through triggering A2BAR signaling on intestinal epithelial cells

2021 ◽  
Author(s):  
Darine W. El-Naccache ◽  
Fei Chen ◽  
Mark Palma ◽  
Alexander Lemenze ◽  
Wenhui Wu ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Extracellular Atp ◽  
Primary Response ◽  
Intestinal Epithelial ◽  
Intestinal Immunity ◽  
Heligmosomoides Polygyrus ◽  
Intestinal Nematode ◽  
Nematode Parasites ◽  
Type 2 Immunity

AbstractMulticellular intestinal nematode parasites can cross the epithelial barrier potentially causing tissue damage and release of danger associated molecular patterns (DAMPs) that may promote type 2 responses and host protective immunity. We investigated whether adenosine specifically binding the A2B adenosine receptor (A2BAR) on epithelial cells played an important role in driving intestinal immunity. Specific blockade of epithelial cell A2BAR inhibited the host protective memory response to the enteric helminth, Heligmosomoides polygyrus bakeri, including disruption of granuloma development at the host:parasite interface during the transient tissue dwelling larval stage. Memory T cell development was blocked during the primary response and transcriptional analyses revealed profound impairment of A2BAR signaling in epithelial cells and reduced type 2 markers by 24 hours after inoculation. Extracellular ATP was visualized by 24 hours after inoculation and shown in CD39 deficient mice to be critical for the adenosine production mediating initiation of type 2 immunity.

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