Excretory/secretory products of adult Haemonchus contortus and Teladorsagia circumcincta which increase the permeability of Caco-2 cell monolayers are neutralised by antibodies from immune hosts

Rehman, Zia Ur; Deng, Qing; Umair, Saleh; Savoian, Matthew S.; Knight, Jacqueline S.; Pernthaner, A.; Simpson, H.V.

doi:10.1016/j.vetpar.2016.03.017

Cited by 14 publications

(15 citation statements)

References 38 publications

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“…A report in 2005 described increased vacuolation and loss of cell contact by HeLa cells following exposure to the excretory/secretory products of the sheep nematode parasites Haemonchus contortus and Ostertagia circumcincta 24 . Interestingly, both products were reported to increase the permeability of Caco-2 cell monolayers, through re-distribution of the tight junction proteins zona occludens-1 and occludin 25 . We hypothesise that components of helminth antigens can alter the permeability of Caco-2 cells and the migration and invasion of cervical cancer cells through modulation of cell surface markers common to formation of tight junctions and the EMT process.…”

Section: Discussionmentioning

confidence: 99%

Hookworm exposure decreases human papillomavirus uptake and cervical cancer cell migration through systemic regulation of epithelial-mesenchymal transition marker expression

Jacobs

Chetty

Horsnell

et al. 2018

Sci Rep

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Persistent infection with human papillomavirus (HPV) is responsible for nearly all new cervical cancer cases worldwide. In low- and middle-income countries (LMIC), infection with helminths has been linked to increased HPV prevalence. As the incidence of cervical cancer rises in helminth endemic regions, it is critical to understand the interaction between exposure to helminths and the progression of cervical cancer. Here we make use of several cervical cancer cell lines to demonstrate that exposure to antigens from the hookworm N. brasiliensis significantly reduces cervical cancer cell migration and global expression of vimentin and N-cadherin. Importantly, N. brasiliensis antigen significantly reduced expression of cell-surface vimentin, while decreasing HPV type 16 (HPV16) pseudovirion internalization. In vivo infection with N. brasiliensis significantly reduced vimentin expression within the female genital tract, confirming the relevance of these in vitro findings. Together, these findings demonstrate that infection with the hookworm-like parasite N. brasiliensis can systemically alter genital tract mesenchymal markers in a way that may impair cervical cancer cell progression. These findings reveal a possible late-stage treatment for reducing cervical cancer progression using helminth antigens.

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Section: Discussionmentioning

confidence: 99%

Hookworm exposure decreases human papillomavirus uptake and cervical cancer cell migration through systemic regulation of epithelial-mesenchymal transition marker expression

Jacobs

Chetty

Horsnell

et al. 2018

Sci Rep

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“…circumcincta and H . contortus increased epithelial permeability of model epithelial cells (Caco-2 cells) in vitro [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

“…contortus ES products also inhibited secretion of histamine (an acid secretogogue) by cultured enterochromaffin-like (ECL) cells [ 45 ]. Direct effects of ES products on parietal cells could be enhanced by their ability to increase mucosal permeability [ 46 ].…”

Section: Introductionmentioning

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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“…The E/S products from the nematodes Haemonchus contortus and Teladorsagia circumcincta when applied to the apical surface of monolayers of the human colon-derived Caco2 epithelial cell line lowered the TER by »20% 2 hours post-treatment. 42 Caco2 monolayers typically have TER values of 250-300 V.cm 2 and so in the absence of data on other markers of paracellular permeability it is difficult to determine the functional significance of the E/S-evoked 20% drop in TER. The TER gradually recovered over a 24-hour period but remained lower than that in time-matched na€ ıve monolayers; immunolocalization at 4 hours post-treatment revealed less peri-junctional staining of ZO-1 and occludin, with the latter showing a diffuse cytoplasmic distribution.…”

Section: Increased Epithelial Permeability Triggered By Infection Witmentioning

confidence: 99%

“…The TER gradually recovered over a 24-hour period but remained lower than that in time-matched na€ ıve monolayers; immunolocalization at 4 hours post-treatment revealed less peri-junctional staining of ZO-1 and occludin, with the latter showing a diffuse cytoplasmic distribution. 42 Hiemstra et al showed that a glycan component of E/S products from the nematode Trichuris suis dose-dependently decreased the electrical impedance (analogous to TER) across monolayers of the mouse cecal CMT93/69 epithelial line and increased the flux of FITC-dextrans (10-100 kDa): this was associated with reduced mRNA for claudin-4 and a claudin-like protein the authors designated epithelial membrane protein-1 (but not claudin-3 or ZO-1) and was not accompanied by increased epithelial cell death. 43 This study also showed that the barrier defect permitted T. suis E/S products to cross the epithelial layer.…”

Section: Increased Epithelial Permeability Triggered By Infection Witmentioning

confidence: 99%

Helminths and intestinal barrier function

2017

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Approximately one-sixth of the worlds' population is infected with helminths and this class of parasite takes a major toll on domestic livestock. The majority of species of parasitic helminth that infect mammals live in the gut (the only niche for tapeworms) where they contact the hosts' epithelial cells. Here, the helminth-intestinal epithelial interface is reviewed in terms of the impact on, and regulation of epithelial barrier function, both intrinsic (epithelial permeability) and extrinsic (mucin, bacterial peptides, commensal bacteria) elements of the barrier. The data available on direct effects of helminths on epithelial permeability are scant, fragmentary and pales in comparison with knowledge of mobilization of immune reactions and effector cells in response to helminth parasites and how these impact intestinal barrier function. The interaction of helminth-host and helminthhost-bacteria is an important determinant of gut form and function and precisely defining these interactions will radically alter our understanding of normal gut physiology and pathophysiological reactions, revealing new approaches to infection with parasitic helminths, bacterial pathogens and idiopathic auto-inflammatory disease.

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Excretory/secretory products of adult Haemonchus contortus and Teladorsagia circumcincta which increase the permeability of Caco-2 cell monolayers are neutralised by antibodies from immune hosts

Cited by 14 publications

References 38 publications

Hookworm exposure decreases human papillomavirus uptake and cervical cancer cell migration through systemic regulation of epithelial-mesenchymal transition marker expression

Hookworm exposure decreases human papillomavirus uptake and cervical cancer cell migration through systemic regulation of epithelial-mesenchymal transition marker expression

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

Helminths and intestinal barrier function

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