scholarly journals Characterisation of Trichuris muris secreted proteins and extracellular vesicles provides new insights into host-parasite communication

2017 ◽  
Author(s):  
Ramon M. Eichenberger ◽  
Md Hasanuzzaman Talukder ◽  
Matthew A. Field ◽  
Phurpa Wangchuk ◽  
Paul Giacomin ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Control Measures ◽  
Host Cells ◽  
Parasitic Nematodes ◽  
Trichuris Muris ◽  
Future Studies ◽  
Secretory Products ◽  
Host Parasite ◽  
First Time ◽  
Host Tissues

AbstractWhipworms are parasitic nematodes that live in the gut of more than 500 million people worldwide. Due to the difficulty in obtaining parasite material, the mouse whipworm Trichuris muris has been extensively used as a model to study human whipworm infections. These nematodes secrete a multitude of compounds that interact with host tissues where they orchestrate a parasitic existence. Herein we provide the first comprehensive characterisation of the excretory/secretory products of T. muris. We identify 148 proteins secreted by T. muris and show for the first time that the mouse whipworm secretes exosome-like extracellular vesicles (EVs) that can interact with host cells. We use an Optiprep® gradient to purify the EVs, highlighting the suitability of this method for purifying EVs secreted by a parasitic nematode. We also characterise the proteomic and genomic content of the EVs, identifying >350 proteins, 56 miRNAs (22 novel) and 475 full-length mRNA transcripts mapping to T. muris gene models. Many of the miRNAs putatively mapped to mouse genes involved in regulation of inflammation, implying a role in parasite-driven immunomodulation. In addition, for the first time to our knowledge, we use colonic organoids to demonstrate the internalisation of parasite EVs by host cells. Understanding how parasites interact with their host is crucial to develop new control measures. This first characterisation of the proteins and EVs secreted by T. muris provides important information on whipworm-host communication and forms the basis for future studies.

scholarly journals Recognition Pattern of the Fasciola hepatica Excretome/Secretome during the Course of an Experimental Infection in Sheep by 2D Immunoproteomics

Pathogens ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 725
Author(s):  
David Becerro-Recio ◽  
Javier González-Miguel ◽  
Alberto Ucero ◽  
Javier Sotillo ◽  
Álvaro Martínez-Moreno ◽  
...  
Keyword(s):  
Experimental Infection ◽  
Fasciola Hepatica ◽  
Cathepsin L ◽  
Helminth Parasites ◽  
Glutathione S Transferase ◽  
Serum Samples ◽  
Secretory Products ◽  
Immunogenic Proteins ◽  
Host Parasite ◽  
First Time

Excretory/secretory products released by helminth parasites have been widely studied for their diagnostic utility, immunomodulatory properties, as well as for their use as vaccines. Due to their location at the host/parasite interface, the characterization of parasite secretions is important to unravel the molecular interactions governing the relationships between helminth parasites and their hosts. In this study, the excretory/secretory products from adult worms of the trematode Fasciola hepatica (FhES) were employed in a combination of two-dimensional electrophoresis, immunoblot and mass spectrometry, to analyze the immune response elicited in sheep during the course of an experimental infection. Ten different immunogenic proteins from FhES recognized by serum samples from infected sheep at 4, 8, and/or 12 weeks post-infection were identified. Among these, different isoforms of cathepsin L and B, peroxiredoxin, calmodulin, or glutathione S-transferase were recognized from the beginning to the end of the experimental infection, suggesting their potential role as immunomodulatory antigens. Furthermore, four FhES proteins (C2H2-type domain-containing protein, ferritin, superoxide dismutase, and globin-3) were identified for the first time as non-immunogenic proteins. These results may help to further understand host/parasite relationships in fasciolosis, and to identify potential diagnostic molecules and drug target candidates of F. hepatica.

scholarly journals Defining the early stages of intestinal colonisation by whipworms

2020 ◽  
Author(s):  
María A. Duque-Correa ◽  
David Goulding ◽  
Claire Cormie ◽  
Catherine Sharpe ◽  
Judit Gali Moya ◽  
...  
Keyword(s):  
Intestinal Epithelium ◽  
Early Stage ◽  
Proximal Colon ◽  
Host Cells ◽  
Parasitic Nematodes ◽  
Metazoan Parasites ◽  
Multiple Cells ◽  
First Time

ABSTRACTHundreds of millions of people are infected with whipworms (Trichuris trichiura), large metazoan parasites that live in the caecum and proximal colon. Whipworms inhabit distinct multi-intracellular epithelial burrows that have been described as syncytial tunnels. However, the interactions between first-stage (L1) larvae and the host epithelia that determine parasite invasion and establishment in the syncytium remain unclear. In vivo experiments investigating these events have been severely hampered by the limited in situ accessibility to intracellular infective larvae at the bottom of the crypts of Lieberkühn, and the lack of genetic tools such as fluorescent organisms that are readily available for other pathogens but not parasitic nematodes. Moreover, cell lines, which do not mimic the complexity of the intestinal epithelium, have been unsuccessful in supporting infection by whipworm larvae. Here, we show that caecaloids grown in an open crypt-like conformation recapitulate the caecal epithelium. Using this system, we establish in vitro infections with T. muris L1 larvae for the first-time, and provide clear evidence that syncytial tunnels are formed at this early stage. We show that larval whipworms are completely intracellular but woven through multiple cells. Using the caecaloids, we are able to visualise the pathways taken by the larvae as they burrow through the epithelial cells. We also demonstrate that larvae degrade the mucus layers overlaying the epithelium, enabling them to access the cells below. We show that early syncytial tunnels are composed of enterocytes and goblet cells that are alive and actively interacting with the larvae during the first 24 h of the infection. Progression of infection results in damage to host cells and by 72 h post-infection, we show that desmosomes of cells from infected epithelium widen and some host cells appear to become liquified. Collectively, our work unravels processes mediating the intestinal epithelium invasion by whipworms and reveals new specific interactions between the host and the parasite that allow the whipworm to establish on its multi-intracellular niche. Our study demonstrates that caecaloids can be used as a relevant in vitro model to investigate the infection biology of T. muris during the early colonisation of its host.

scholarly journals Characterization of Trichuris muris secreted proteins and extracellular vesicles provides new insights into host–parasite communication

2018 ◽  
Vol 7 (1) ◽  
pp. 1428004 ◽  
Author(s):  
Ramon M. Eichenberger ◽  
Md Hasanuzzaman Talukder ◽  
Matthew A. Field ◽  
Phurpa Wangchuk ◽  
Paul Giacomin ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Secreted Proteins ◽  
Trichuris Muris ◽  
Host Parasite

Host–parasite relationships and development of the ergot sclerotium in Claviceps purpurea

1980 ◽  
Vol 58 (8) ◽  
pp. 942-958 ◽  
Author(s):  
E. S. Luttrell
Keyword(s):  
Vascular Bundle ◽  
Secale Cereale ◽  
Epidermal Cells ◽  
Host Cells ◽  
Claviceps Purpurea ◽  
Conducting Tissue ◽  
Storage Cells ◽  
Host Parasite ◽  
Central Strand ◽  
Host Tissues

Conidia of Claviceps purpurea germinate on the stigmas of Secale cereale, and intercellular hyphae grow downward through the style and inner wall of the ovary to the tip of the rachilla. Across the tip of the rachilla, hyphae surrounding living host cells form a narrow interface that plunges downward into the central vascular bundle approximately to the level of origin of the lodicules. This biotrophic relationship is well established 5–6 days after infection at anthesis and persists unaltered through maturation of the ergot sclerotium at approximately the 28th day. Tissues in the base of the ovary above this interface are destroyed and replaced by fungus stroma. Xylem vessels in the tip of the rachilla are destroyed and replaced by a hyphal core extending downward from the stromatic foot of the fungus. Hyphae emerging between the epidermal cells of the ovary form an external matrix that contributes to further expansion of the stroma. A palisade of phialidic conidiophores develops over the surface of the stroma, which is involuted into labyrinthine chambers. Conidia ooze from the florets in drops of honeydew by the 6th or 7th day. The ovarian cap and the upper part of the ovule are pushed upward on the apex of the conidial stroma, and some of these isolated host cells remain alive until the 11th day. A layer of vertically arranged parallel hyphae across the base of the conidial stroma forms a generative zone that sharply delimits the basal stromatic foot seated in the floret and by apically directed intercalary growth produces the compact tissues of the ergot sclerotium. The sclerotium begins to protrude from the floret by the 11th day. The withered remnants of the conidial stroma and the ovarian cap are carried upward on the tip of the massive sclerotium. Beneath the dark rind the hyaline tissue of the sclerotium consists primarily of compacted, isodiametric storage cells. A loose hyphal conducting tissue forms a central strand from which narrow vanes radiate irregularly toward the periphery. Ergot of rye is a replacement disease in which the parasite disintegrates host tissues in areas required for development of its own structures while maintaining a compatible relationship with adjacent host cells as a source of water and nutrients.

scholarly journals Schistosoma haematobium Extracellular Vesicle Proteins Confer Protection in a Heterologous Model of Schistosomiasis

Vaccines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 416 ◽  
Author(s):  
Gebeyaw G. Mekonnen ◽  
Bemnet A. Tedla ◽  
Darren Pickering ◽  
Luke Becker ◽  
Lei Wang ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Schistosoma Haematobium ◽  
Extracellular Vesicle ◽  
Surface Proteins ◽  
Helminth Parasites ◽  
Glutathione S Transferase ◽  
Heterologous Challenge ◽  
Host Parasite ◽  
Host Tissues ◽  
Vesicle Proteins

Helminth parasites release extracellular vesicles which interact with the surrounding host tissues, mediating host–parasite communication and other fundamental processes of parasitism. As such, vesicle proteins present attractive targets for the development of novel intervention strategies to control these parasites and the diseases they cause. Herein, we describe the first proteomic analysis by LC-MS/MS of two types of extracellular vesicles (exosome-like, 120 k pellet vesicles and microvesicle-like, 15 k pellet vesicles) from adult Schistosoma haematobium worms. A total of 57 and 330 proteins were identified in the 120 k pellet vesicles and larger 15 k pellet vesicles, respectively, and some of the most abundant molecules included homologues of known helminth vaccine and diagnostic candidates such as Sm-TSP2, Sm23, glutathione S-transferase, saponins and aminopeptidases. Tetraspanins were highly represented in the analysis and found in both vesicle types. Vaccination of mice with recombinant versions of three of these tetraspanins induced protection in a heterologous challenge (S. mansoni) model of infection, resulting in significant reductions (averaged across two independent trials) in liver (47%, 38% and 41%) and intestinal (47%, 45% and 41%) egg burdens. These findings offer insight into the mechanisms by which anti-tetraspanin antibodies confer protection and highlight the potential that extracellular vesicle surface proteins offer as anti-helminth vaccines.

scholarly journals A Deep Exploration of the Transcriptome and “Excretory/Secretory” Proteome of Adult Fascioloides magna

2012 ◽  
Vol 11 (11) ◽  
pp. 1340-1353 ◽  
Author(s):  
Cinzia Cantacessi ◽  
Jason Mulvenna ◽  
Neil D. Young ◽  
Martin Kasny ◽  
Petr Horak ◽  
...  
Keyword(s):  
Biological Pathway ◽  
Fascioloides Magna ◽  
Protein Motifs ◽  
Sds Page ◽  
Antioxidant Proteins ◽  
Secretory Products ◽  
Liver Flukes ◽  
Host Parasite ◽  
Deep Exploration ◽  
First Time

Parasitic liver flukes of the family Fasciolidae are responsible for major socioeconomic losses worldwide. However, at present, knowledge of the fundamental molecular biology of these organisms is scant. Here, we characterize, for the first time, the transcriptome and secreted proteome of the adult stage of the “giant liver fluke,” Fascioloides magna, using Illumina sequencing technology and one-dimensional SDS-PAGE and OFFGEL protein electrophoresis, respectively. A total of ∼54,000,000 reads were generated and assembled into ∼39,000 contiguous sequences (contigs); ∼20,000 peptides were predicted and classified based on homology searches, protein motifs, gene ontology, and biological pathway mapping. From the predicted proteome, 48.1% of proteins could be assigned to 384 biological pathway terms, including “spliceosome,” “RNA transport,” and “endocytosis.” Putative proteins involved in amino acid degradation were most abundant. Of the 835 secreted proteins predicted from the transcriptome of F. magna, 80 were identified in the excretory/secretory products from this parasite. Highly represented were antioxidant proteins, followed by peptidases (particularly cathepsins) and proteins involved in carbohydrate metabolism. The integration of transcriptomic and proteomic datasets generated herein sets the scene for future studies aimed at exploring the potential role(s) that molecules might play at the host–parasite interface and for establishing novel strategies for the treatment or control of parasitic fluke infections.

scholarly journals Schistosoma haematobium extracellular vesicle proteins confer protection in a heterologous model of schistosomiasis

2020 ◽  
Author(s):  
Gebeyaw G. Mekonnen ◽  
Bemnet A. Tedla ◽  
Darren Pickering ◽  
Luke Becker ◽  
Lei Wang ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Schistosoma Haematobium ◽  
Extracellular Vesicle ◽  
Surface Proteins ◽  
Helminth Parasites ◽  
Heterologous Challenge ◽  
Host Parasite ◽  
Insight Into ◽  
Host Tissues ◽  
Vesicle Proteins

AbstractHelminth parasites release extracellular vesicles which interact with the surrounding host tissues, mediating host-parasite communication and other fundamental processes of parasitism. As such, vesicle proteins present attractive targets for the development of novel intervention strategies to control these parasites and the diseases they cause. Herein, we describe the first proteomic analysis by LC-MS/MS of two types of extracellular vesicles (exosome-like, 120k pellet vesicles and microvesicle-like, 15k pellet vesicles) from adult Schistosoma haematobium worms. A total of 57 and 330 proteins were identified in the 120k pellet vesicles and larger 15k pellet vesicles, respectively, and some of the most abundant molecules included homologues of known helminth vaccine and diagnostic candidates such as Sm-TSP2, Sm23, glutathione S-tranferase, saposins and aminopeptidases. Tetraspanins were highly represented in the analysis and found in both vesicle types. Vaccination of mice with recombinant versions of three of these tetraspanins induced protection in a heterologous challenge (S. mansoni) model of infection, resulting in significant reductions (averaged across two independent trials) in liver (47%, 38% and 41%) and intestinal (47%, 45% and 41%) egg burdens. These findings offer insight into the mechanisms by which anti-tetraspanin antibodies confer protection and highlight the potential that extracellular vesicle surface proteins offer as anti-helminth vaccines.

scholarly journals Not so sterile after all: The endomicrobiome of plerocercoids of the cestode parasiteSchistocephalus solidusand changes to the microbiome of its Threespine Stickleback host

2018 ◽  
Author(s):  
Megan Hahn ◽  
Nolwenn Dheilly
Keyword(s):  
Horizontal Transmission ◽  
Body Cavity ◽  
The Body ◽  
Schistocephalus Solidus ◽  
Host Parasite Interactions ◽  
Host Parasite ◽  
First Time ◽  
Host Tissues

AbstractDespite the growing recognition of the role of bacteria in animal biology, the microbiome of parasites remains largely unexplored. In particular, the presence of bacteria in tapeworms has never been investigated and parasites that exit the intestine would be considered sterile. We characterized for the first time the microbiome of a tapeworm.Schistocephalus solidusplerocercoids, collected from the body cavity of its stickleback host, were found to harbor a complex microbiome. The most abundant and the most prevalent bacteria wasPolynucleobacter sp.. In addition,S. solidusinfection was associated significant changes in the stickleback host gut microbiome with an increase in microbial load and changes in diversity and composition. Finally, the same bacteria were often found inS. solidusand the stomach and intestine of the corresponding hosts, a result that highlights the importance of characterizing the microbiome of host tissues and parasites from the same individuals to assess the potential for horizontal transmission of microbes. This study clearly emphasizes the need for further characterization of the microbiome of a broad range of parasites and for studies to determine the ecological, evolutionary and functional role that microbes play in host-parasite interactions.

scholarly journals Helicobacter pylori Outer Membrane Vesicles and Extracellular Vesicles from Helicobacter pylori-Infected Cells in Gastric Disease Development

2021 ◽  
Vol 22 (9) ◽  
pp. 4823
Author(s):  
María Fernanda González ◽  
Paula Díaz ◽  
Alejandra Sandoval-Bórquez ◽  
Daniela Herrera ◽  
Andrew F. G. Quest
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Outer Membrane ◽  
Extracellular Vesicles ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Host Cells ◽  
Gastric Epithelium ◽  
Infected Cells ◽  
H Pylori

Extracellular vesicles (EVs) are cell-derived vesicles important in intercellular communication that play an essential role in host-pathogen interactions, spreading pathogen-derived as well as host-derived molecules during infection. Pathogens can induce changes in the composition of EVs derived from the infected cells and use them to manipulate their microenvironment and, for instance, modulate innate and adaptive inflammatory immune responses, both in a stimulatory or suppressive manner. Gastric cancer is one of the leading causes of cancer-related deaths worldwide and infection with Helicobacter pylori (H. pylori) is considered the main risk factor for developing this disease, which is characterized by a strong inflammatory component. EVs released by host cells infected with H. pylori contribute significantly to inflammation, and in doing so promote the development of disease. Additionally, H. pylori liberates vesicles, called outer membrane vesicles (H. pylori-OMVs), which contribute to atrophia and cell transformation in the gastric epithelium. In this review, the participation of both EVs from cells infected with H. pylori and H. pylori-OMVs associated with the development of gastric cancer will be discussed. By deciphering which functions of these external vesicles during H. pylori infection benefit the host or the pathogen, novel treatment strategies may become available to prevent disease.

scholarly journals Lipoproteins Are Responsible for the Pro-Inflammatory Property of Staphylococcus aureus Extracellular Vesicles

2021 ◽  
Vol 22 (13) ◽  
pp. 7099
Author(s):  
Pradeep Kumar Kopparapu ◽  
Meghshree Deshmukh ◽  
Zhicheng Hu ◽  
Majd Mohammad ◽  
Marco Maugeri ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Inflammatory Responses ◽  
Surface Proteins ◽  
Host Cells ◽  
Immune Stimulation ◽  
Domains Of Life ◽  
Major Surface ◽  
Staphylococcal Aureus

Staphylococcal aureus (S. aureus), a Gram-positive bacteria, is known to cause various infections. Extracellular vesicles (EVs) are a heterogeneous array of membranous structures secreted by cells from all three domains of life, i.e., eukaryotes, bacteria, and archaea. Bacterial EVs are implied to be involved in both bacteria–bacteria and bacteria–host interactions during infections. It is still unclear how S. aureus EVs interact with host cells and induce inflammatory responses. In this study, EVs were isolated from S. aureus and mutant strains deficient in either prelipoprotein lipidation (Δlgt) or major surface proteins (ΔsrtAB). Their immunostimulatory capacities were assessed both in vitro and in vivo. We found that S. aureus EVs induced pro-inflammatory responses both in vitro and in vivo. However, this activity was dependent on lipidated lipoproteins (Lpp), since EVs isolated from the Δlgt showed no stimulation. On the other hand, EVs isolated from the ΔsrtAB mutant showed full immune stimulation, indicating the cell wall anchoring of surface proteins did not play a role in immune stimulation. The immune stimulation of S. aureus EVs was mediated mainly by monocytes/macrophages and was TLR2 dependent. In this study, we demonstrated that not only free Lpp but also EV-imbedded Lpp had high pro-inflammatory activity.

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