IL-4/IL-13 independent goblet cell hyperplasia in experimental helminth infections

Marillier, Reece; Michels, Chesney; Smith, Elizabeth M.; Fick, Lizette; Leeto, Mosiuoa; Dewals, Benjamin G; Horsnell, William; Brombacher, Frank

doi:10.1186/1471-2172-9-11

Cited by 57 publications

(48 citation statements)

References 41 publications

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“…This includes type 2 cytokines such as IL-13 and IL-4 [37], [38], but also pro-inflammatory cytokines such as TNF and IL-1 [39], [40]. Although IL-13 and IL-4 are believed to be the key driver cytokines for the induction of goblet cell hyperplasia during helminth infections [41], [42], [43], some studies have demonstrated IL-4/13-independent goblet cell hyperplasia [44]. Furthermore, increase in intestinal Muc2 and Muc3 expression during infection with the nematode Trichinella spiralis has been reported in IL-4-deficient mice [45].…”

Section: Resultsmentioning

confidence: 99%

IL-22 Mediates Goblet Cell Hyperplasia and Worm Expulsion in Intestinal Helminth Infection

Turner¹,

Stockinger²,

2013

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Type 2 immune responses are essential in protection against intestinal helminth infections. In this study we show that IL-22, a cytokine important in defence against bacterial infections in the intestinal tract, is also a critical mediator of anti-helminth immunity. After infection with Nippostrongylus brasiliensis, a rodent hookworm, IL-22-deficient mice showed impaired worm expulsion despite normal levels of type 2 cytokine production. The impaired worm expulsion correlated with reduced goblet cell hyperplasia and reduced expression of goblet cell markers. We further confirmed our findings in a second nematode model, the murine whipworm Trichuris muris. T.muris infected IL-22-deficient mice had a similar phenotype to that seen in N.brasiliensis infection, with impaired worm expulsion and reduced goblet cell hyperplasia. Ex vivo and in vitro analysis demonstrated that IL-22 is able to directly induce the expression of several goblet cell markers, including mucins. Taken together, our findings reveal that IL-22 plays an important role in goblet cell activation, and thus, a key role in anti-helminth immunity.

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Section: Resultsmentioning

confidence: 99%

IL-22 Mediates Goblet Cell Hyperplasia and Worm Expulsion in Intestinal Helminth Infection

Turner¹,

Stockinger²,

2013

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“…That the intestinal goblet cells are under direct regulation by the immune system is best exemplified by the striking goblet cell hyperplasia and mucus hypersecretion associated with parasitic helminth infections (54;55). These infections elicit a T helper type 2 (Th2) response with increased levels of cytokines such as interleukin IL-4, IL-5, IL-9 and IL-13, where IL-13 is considered the major effector cytokine.…”

Section: Immune Regulation Of Goblet Cell Functionmentioning

confidence: 99%

New developments in goblet cell mucus secretion and function

et al. 2015

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Goblet cells and their main secretory product, mucus, have long been poorly appreciated; however, recent discoveries have changed this and placed these cells at the center stage of our understanding of mucosal biology and the immunology of the intestinal tract. The mucus system differs substantially between the small and large intestine, although it is built around MUC2 mucin polymers in both cases. Furthermore, that goblet cells and the regulation of their secretion also differ between these two parts of the intestine is of fundamental importance for a better understanding of mucosal immunology. There are several types of goblet cell which can be delineated based on their location and function. The surface colonic goblet cells secrete continuously to maintain the inner mucus layer, whereas goblet cells of the colonic and small intestinal crypts secrete upon stimulation, for example after endocytosis or in response to acetyl choline. However, despite much progress in recent years our understanding of goblet cell function and regulation is still in its infancy.

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“…For example, a study conducted by Marillier and colleagues demonstrated goblet cell hyperplasia is observed independent of the IL‐13/IL‐4 signalling apparatus,62 and Muc2 and Muc3 transcripts were augmented even in the absence of IL‐4 during T. spiralis infection 50. Furthermore, inflammatory cytokines have been implicated to have a role in goblet cell function during parasitic infection, including IL‐1, TNF and IL‐22,63, 64, 65 and it is yet to be defined if microbial factors, the inflammasome and adrenergic and cholinergic receptors can influence the secretion of mucins and other goblet cell‐associated products during parasitic invasion.…”

Section: Immune Control Against Gi Nematode Infectionmentioning

confidence: 99%

A sticky end for gastrointestinal helminths; the role of the mucus barrier

Sharpe

Thornton

Grencis

2018

Parasite Immunology

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SummaryGastrointestinal (GI) nematodes are a group of successful multicellular parasites that have evolved to coexist within the intestinal niche of multiple species. It is estimated that over 10% of the world's population are chronically infected by GI nematodes, making this group of parasitic nematodes a major burden to global health. Despite the large number of affected individuals, there are few effective treatments to eradicate these infections. Research into GI nematode infections has primarily focused on defining the immunological and pathological consequences on host protection. One important but neglected aspect of host protection is mucus, and the concept that mucus is just a simple barrier is no longer tenable. In fact, mucus is a highly regulated and dynamic‐secreted matrix, underpinned by a physical hydrated network of highly glycosylated mucins, which is increasingly recognized to have a key protective role against GI nematode infections. Unravelling the complex interplay between mucins, the underlying epithelium and immune cells during infection are a major challenge and are required to fully define the protective role of the mucus barrier. This review summarizes the current state of knowledge on mucins and the mucus barrier during GI nematode infections, with particular focus on murine models of infection.

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IL-4/IL-13 independent goblet cell hyperplasia in experimental helminth infections

Cited by 57 publications

References 41 publications

IL-22 Mediates Goblet Cell Hyperplasia and Worm Expulsion in Intestinal Helminth Infection

IL-22 Mediates Goblet Cell Hyperplasia and Worm Expulsion in Intestinal Helminth Infection

New developments in goblet cell mucus secretion and function

A sticky end for gastrointestinal helminths; the role of the mucus barrier

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