Enteric epithelial cells support growth of Hymenolepis diminuta in vitro and trigger TH2-promoting events in a species-specific manner

Lopes, Fernando; Reyes, José L.; Wang, Arthur; Leung, Gabriella; McKay, Derek M.

doi:10.1016/j.ijpara.2015.05.004

Cited by 12 publications

(10 citation statements)

References 24 publications

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“…In addition, using the reductionist approach of culturing a single H . diminuta scolex with epithelial cell lines, we found epithelia from the non-permissive mouse host produced IL-25, IL-33 and TSLP (mRNA and protein) and that the rat (permissive host) IEC.6 cell line failed to show this alarmin response to the worm [ 36 ]. Of note, qPCR revealed a trend towards increased IL-33 and thymic stromal lymphopoietin (TSLP) mRNA expression in the jejunum of H .…”

Section: Resultsmentioning

confidence: 99%

IL-22 Restrains Tapeworm-Mediated Protection against Experimental Colitis via Regulation of IL-25 Expression

et al. 2016

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Interleukin (IL)-22, an immune cell-derived cytokine whose receptor expression is restricted to non-immune cells (e.g. epithelial cells), can be anti-inflammatory and pro-inflammatory. Mice infected with the tapeworm Hymenolepis diminuta are protected from dinitrobenzene sulphonic acid (DNBS)-induced colitis. Here we assessed expulsion of H. diminuta, the concomitant immune response and the outcome of DNBS-induced colitis in wild-type (WT) and IL-22 deficient mice (IL-22-/-) ± infection. Interleukin-22-/- mice had a mildly impaired ability to expel the worm and this correlated with reduced or delayed induction of TH2 immunity as measured by splenic and mesenteric lymph node production of IL-4, IL-5 and IL-13 and intestinal Muc-2 mRNA and goblet cell hyperplasia; in contrast, IL-25 increased in the small intestine of IL-22-/- mice 8 and 12 days post-infection compared to WT mice. In vitro experiments revealed that H. diminuta directly evoked epithelial production of IL-25 that was inhibited by recombinant IL-22. Also, IL-10 and markers of regulatory T cells were increased in IL-22-/- mice that displayed less DNBS (3 mg, ir. 72h)-induced colitis. Wild-type mice infected with H. diminuta were protected from colitis, as were infected IL-22-/- mice and the latter to a degree that they were almost indistinguishable from control, non-DNBS treated mice. Finally, treatment with anti-IL-25 antibodies exaggerated DNBS-induced colitis in IL-22-/- mice and blocked the anti-colitic effect of infection with H. diminuta. Thus, IL-22 is identified as an endogenous brake on helminth-elicited TH2 immunity, reducing the efficacy of expulsion of H. diminuta and limiting the effectiveness of the anti-colitic events mobilized following infection with H. diminuta in a non-permissive host.

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Section: Resultsmentioning

confidence: 99%

IL-22 Restrains Tapeworm-Mediated Protection against Experimental Colitis via Regulation of IL-25 Expression

et al. 2016

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“…This can result in the release of alarmins from the enterocyte (e.g., interleukin (IL)-25), the promotion of T helper-2 (TH2) type immunity and upregulation of effector mechanisms (e.g., IL-5 evoked eosinophils) aimed at worm destruction and expulsion. 32,33 However, the corollary of this is that helminths are adept at manipulating immunity in their hosts to meet their own needs, 34 and do so via the release of molecules that may need to gain access to target cells in the mucosa -a leaky epithelial barrier would facilitate this.…”

Section: Why Consider Epithelial Permeability In the Context Of Infecmentioning

confidence: 99%

“…32,33,[38][39][40][41] Studies in which helminth E/S products are added directly to epithelial monolayers and permeability subsequently assessed are scarce. 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.…”

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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“…Lacking a T-cell receptor, ILCs have been classified as types 1 (Tbet + , IFNγ), 2 (RORα + , IL-4), and 3 (RORγt + , IL-17, IL-22), paralleling Th1, Th2, and Th17 cells, respectively, with the assumption that they fulfil the necessary Th-cell role until Th cells are mobilized. In response to infection with GI helminths, tuft cells release IL-25 that activates ILC2 to release IL-4, which may feed back on to the epithelium to evoke goblet cell hyperplasia and act as a catalyst for Th2 cell polarization [ 21 ] (the transporting epithelial cells may also be a source of IL-25 and other alarmins including IL-33 and thymic stromal lymphopoietin (TSLP)) [ 22 ]. Recently, two distinct subsets of tuft cells were identified based on expression of genes related to neurone development or for Th2 cytokine receptors [ 23 ].…”

Section: Host Immune Activity Following Infection With Helminthsmentioning

confidence: 99%

Modulation of the immune response by helminths: a role for serotonin?

Wang¹,

Sharkey

McKay³

2018

Bioscience Reports

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The mammalian gut is a remarkable organ: with a nervous system that rivals the spinal cord, it is the body’s largest repository of immune and endocrine cells and houses an immense and complex microbiota. Infection with helminth parasites elicits a conserved program of effector and regulatory immune responses to eradicate the worm, limit tissue damage, and return the gut to homeostasis. Discrete changes in the nervous system, and to a lesser extent the enteroendocrine system, occur following helminth infection but the importance of these adaptations in expelling the worm is poorly understood. Approximately 90% of the body’s serotonin (5-hydroxytryptamine (5-HT)) is made in enterochromaffin (EC) cells in the gut, indicative of the importance of this amine in intestinal function. Signaling via a plethora of receptor subtypes, substantial evidence illustrates that 5-HT affects immunity. A small number of studies document changes in 5-HT levels following infection with helminth parasites, but these have not been complemented by an understanding of the role of 5-HT in the host–parasite interaction. In reviewing this area, the gap in knowledge of how changes in the enteric serotonergic system affects the outcome of infection with intestinal helminths is apparent. We present this as a call-to-action by investigators in the field. We contend that neuronal EC cell–immune interactions in the gut are essential in maintaining homeostasis and, when perturbed, contribute to pathophysiology. The full affect of infection with helminth parasites needs to define, and then mechanistically dissect the role of the enteric nervous and enteroendocrine systems of the gut.

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Enteric epithelial cells support growth of Hymenolepis diminuta in vitro and trigger TH2-promoting events in a species-specific manner

Cited by 12 publications

References 24 publications

IL-22 Restrains Tapeworm-Mediated Protection against Experimental Colitis via Regulation of IL-25 Expression

IL-22 Restrains Tapeworm-Mediated Protection against Experimental Colitis via Regulation of IL-25 Expression

Helminths and intestinal barrier function

Modulation of the immune response by helminths: a role for serotonin?

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