Excretory/secretory products of sheep abomasal nematode parasites cause vacuolation and increased neutral red uptake by HeLa cells

Przemeck, S.M.C.; Huber, Alexandra; Brown, Simon; Pedley, Kevin C.; Simpson, H.V.

doi:10.1007/s00436-004-1280-8

Cited by 15 publications

(9 citation statements)

References 18 publications

(13 reference statements)

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“…circumcincta and H . contortus chemicals promote vacuolation of HeLa cells in vitro [ 90 , 91 ]. Vacuolation is also a feature of infections of gastric tissue by H .…”

Section: Discussionmentioning

confidence: 99%

Abomasal dysfunction and cellular and mucin changes during infection of sheep with larval or adult Teladorsagia circumcincta

et al. 2017

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This is the first integrated study of the effects on gastric secretion, inflammation and fundic mucins after infection with L3 T. circumcincta and in the very early period following transplantation of adult worms. At 3 months-of-age, 20 Coopworth lambs were infected intraruminally with 35,000 L3; infected animals were killed on Days 5, 10, 15, 20 and 30 post-infection and 6 controls on either Day 0 or 30 post-infection. Another 15 Romney cross lambs received 10,000 adult worms at 4–5 months-of-age though surgically-implanted abomasal cannulae and were killed after 6, 12, 24 and 72 hours; uninfected controls were also killed at 72 hours. Blood was collected at regular intervals from all animals for measurement of serum gastrin and pepsinogen and abomasal fluid for pH measurement from cannulated sheep. Tissues collected at necropsy were fixed in Bouin’s fluid for light microscopy, immunocytochemistry and mucin staining and in Karnovsky's fluid for electron microscopy. Nodules around glands containing developing larvae were seen on Day 5 p.i., but generalised effects on secretion occurred only after parasite emergence and within hours after transplantation of adult worms. After L3 infection, there were maximum worm burdens on Days 10–15 post-infection, together with peak tissue eosinophilia, inhibition of gastric acid secretion, hypergastrinaemia, hyperpepsinogenaemia, loss of parietal cells, enlarged gastric pits containing less mucin and increased numbers of mucous neck cells. After adult transplantation, serum pepsinogen was significantly increased after 9 hours and serum gastrin after 18 hours. Parallel changes in host tissues and the numbers of parasites in the abomasal lumen suggest that luminal parasites, but not those in the tissues, are key drivers of the pathophysiology and inflammatory response in animals exposed to parasites for the first time. These results are consistent with initiation of the host response by parasite chemicals diffusing across the surface epithelium, possibly aided by components of ES products which increased permeability. Parietal cells appear to be a key target, resulting in secondary increases in serum gastrin, pit elongation, loss of surface mucins and inhibition of chief cell maturation. Inflammation occurs in parallel, and could either cause the pathology or exacerbate the direct effects of ES products.

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“…circumcincta and H . contortus chemicals promote vacuolation of HeLa cells in vitro [ 90 , 91 ]. Vacuolation is also a feature of infections of gastric tissue by H .…”

Section: Discussionmentioning

confidence: 99%

Abomasal dysfunction and cellular and mucin changes during infection of sheep with larval or adult Teladorsagia circumcincta

et al. 2017

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“…Recently, it was reported that recombinant H. contortus galectin (rHco-gal-m) inhibited the expression of MHC II molecules, decreased the T cell activation and proliferation, induced apoptosis of T cells and effected several signaling cascades in vitro [10]. In vitro studies also showed that ESPs had direct effects on cultured cells or tissues, such as inhibiting acid secretion [19] and inducing the vacuolation and detachment of HeLa cells [20, 21]. These findings indicated that ESPs might play multiple functions in vivo.…”

Section: Introductionmentioning

confidence: 99%

Haemonchus contortusexcretory and secretory proteins (HcESPs) suppress functions of goat PBMCsin vitro

Gadahi

Ehsan

et al. 2016

Oncotarget

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Excretory and secretory products (ESPs) of nematode contain various proteins which are capable of inducing the instigation or depression of the host immune response and are involved in the pathogenesis of the worms. In the present study, Haemonchus contortus excretory and secretory products (HcESPs) were collected from the adult worms. Binding of HcESPs to goat peripheral blood mononuclear cells (PBMCs) was confirmed by immune-fluorescence assay. Effects of the HcESPs on cytokine production, cell proliferation, cell migration and nitric oxide (NO) production of PBMCs were checked by co-incubation of HcESPs with goat PBMCs. The results indicated that the production of IL-4 and IFN-γ were significantly decreased by HcESPs in dose dependent manner. On the contrary, the production of IL-10 and IL-17 were increased. Cell migration was significantly enhanced by HcESPs, whereas, HcESPs treatment significantly suppressed the cell proliferation and NO production. These results indicated that the HcESPs played important suppressive regulatory roles on PBMCs and provided highlights to the understanding of the host-parasite interactions.

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“…rHco-gal-m inhibits the expression of MHC II molecules, decreases T cell activation and proliferation, induces the apoptosis of T cells and affects several signaling cascades [ 19 ]. In vitro studies have reported that parasitic ESPs have a direct effect on cultured cells or tissues, such as inhibiting acid secretion [ 20 ] and inducing the vacuolation and detachment of HeLa cells [ 21 , 22 ]. These findings indicate that ESPs have multiple functions in vivo .…”

Section: Introductionmentioning

confidence: 99%

Proteomic Analysis of the Excretory and Secretory Proteins of Haemonchus contortus (HcESP) Binding to Goat PBMCs In Vivo Revealed Stage-Specific Binding Profiles

Gadahi¹,

Wang²,

Gao³

et al. 2016

PLoS ONE

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Haemonchus contortus is a parasitic gastrointestinal nematode, and its excretory and secretory products (HcESPs) interact extensively with the host cells. In this study, we report the interaction of proteins from HcESPs at different developmental stages to goat peripheral blood mononuclear cells (PBMCs) in vivo using liquid chromatography-tandem mass spectrometry. A total of 407 HcESPs that interacted with goat PBMCs at different time points were identified from a H. contortus protein database using SEQUEST searches. The L4 and L5 stages of H. contortus represented a higher proportion of the identified proteins compared with the early and late adult stages. Both stage-specific interacting proteins and proteins that were common to multiple stages were identified. Forty-seven interacting proteins were shared among all stages. The gene ontology (GO) distributions of the identified goat PBMC-interacting proteins were nearly identical among all developmental stages, with high representation of binding and catalytic activity. Cellular, metabolic and single-organism processes were also annotated as major biological processes, but interestingly, more proteins were annotated as localization processes at the L5 stage than at the L4 and adult stages. Based on the clustering of homologous proteins, we improved the functional annotations of un-annotated proteins identified at different developmental stages. Some unnamed H. contortus ATP-binding cassette proteins, including ADP-ribosylation factor and P-glycoprotein-9, were identified by STRING protein clustering analysis.

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Excretory/secretory products of sheep abomasal nematode parasites cause vacuolation and increased neutral red uptake by HeLa cells

Cited by 15 publications

References 18 publications

Abomasal dysfunction and cellular and mucin changes during infection of sheep with larval or adult Teladorsagia circumcincta

Abomasal dysfunction and cellular and mucin changes during infection of sheep with larval or adult Teladorsagia circumcincta

Haemonchus contortusexcretory and secretory proteins (HcESPs) suppress functions of goat PBMCsin vitro

Proteomic Analysis of the Excretory and Secretory Proteins of Haemonchus contortus (HcESP) Binding to Goat PBMCs In Vivo Revealed Stage-Specific Binding Profiles

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