T lymphocyte dependent enteropathy in murine <i>Trichinella spiralis</i> infection

Garside, Paul; Grencis, R. K.; Am, Mowat

doi:10.1111/j.1365-3024.1992.tb00462.x

Cited by 68 publications

(66 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Much of this analytical work has used the mouse-Trichinella spiralis model and this has generated hypotheses based on immunologically driven mechanisms of enteropathy, both Th2-mediated (Garside et al, 1992;Lawrence et al, 1998) and, more recently, mediated via innate immunity (McDermott et al, 2005). The key parameters quantified in such studies have been villus height, crypt depth and mucosal cellular division as reflected by mitotic figures.…”

Section: Introductionmentioning

confidence: 99%

The effect of the hookworm Ancylostoma ceylanicum on the mucosal architecture of the small intestine in hamsters

Alkazmi

Dehlawi

Behnke³

2006

J. Helminthol.

View full text Add to dashboard Cite

Hookworms are known to cause marked changes to the intestinal mucosa, especially in relation to erosion of the villi. However, since the development of enteropathy has not been examined thoroughly through quantitative experiments on infected animals, the results of experiments conducted in hamsters infected with Ancylostoma ceylanicum are reported. Changes to intestinal architecture were first apparent between 12 and 14 days after infection, and then increased in intensity for 3-4 weeks, persisting for as long as worms were present (. 63 days). Following infection, the height of villi declined from a mean of 1002 mm in naïve controls to less than 200 mm and as low as 18 mm in one case. The depth of the crypts of Lieberkuhn increased from a baseline value of 166 mm in naïve controls to in excess of 600 mm within 6 weeks of infection. Mitotic figures had a baseline value of 5.5 per villus-crypt unit, and this rose to in excess of 25 in some experiments. Changes were dependent on the intensity of the parasite burden on day 20, but by 30 days after infection changes in all three values were maximal and density-dependent relationships were no longer clearly apparent. Villus height and crypt depth returned to near normal values within a week of the removal of worms, although group means for both remained different from naïve controls for at least 3 weeks after treatment. Cellular division, as reflected in numbers of mitotic figures, stayed elevated for over 5 weeks after removal of worms. The results suggest that enteropathy in hookworm infections stems from a combination of intestinal immune responses and from the grazing activities of the adult worms on the mucosal surface, but is not sufficient per se for expulsion of this parasite.

show abstract

Section: Introductionmentioning

confidence: 99%

The effect of the hookworm Ancylostoma ceylanicum on the mucosal architecture of the small intestine in hamsters

Alkazmi

Dehlawi

Behnke³

2006

J. Helminthol.

View full text Add to dashboard Cite

show abstract

“…T. spiralis elicits a strong T helper 2 response resulting in intestinal goblet cell hyperplasia, eosinophilia, and a profound mucosal mastocytosis (3)(4)(5). Efficient parasite expulsion depends on CD4 ϩ T cells through control of the critical mast cell response (6). In the absence of intestinal mast cells the loss of parasites is markedly delayed (7).…”

mentioning

confidence: 99%

Mast cells disrupt epithelial barrier function during enteric nematode infection

McDermott

Bartram²,

Knight³

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

299

245

View full text Add to dashboard Cite

We have investigated the influence of mast cells on the barrier function of intestinal epithelium during nematode infection. Trichinella spiralis infection induces a strong type 2 cytokinemediated inflammation, resulting in a critical mucosal mastocytosis that is known to mediate expulsion of the parasites from the intestine. The host response to infection is also characterized by an increase in mucosal leakiness. We show here that intestinal epithelial permeability is markedly elevated during infection, with kinetics that mirror the adaptive immune response to primary and secondary infection. Furthermore, we have identified degradation of the tight junction protein, occludin, thereby providing a mechanism for increased paracellular permeability during helminth infection. We further demonstrate by using anti-c-kit antibody and IL-9 transgenic mice that mast cells are directly responsible for increasing epithelial paracellular permeability and that mice deficient in a mast cell-specific protease fail to increase intestinal permeability and fail to expel their parasite burden. These results provide the mechanism whereby mucosal mast cells mediate parasite expulsion from the intestine.T he adult stage of the nematode Trichinella spiralis resides within enterocytes of the jejunum. During parasite infection characteristic changes occur in the small intestine (1). It has long been known that the gut becomes edematous and inflamed, with these responses peaking at the time of parasite expulsion from the host, but the precise mechanisms involved have remained obscure. Infection induces leakiness in the intestinal epithelium that is considered to be a host defense mechanism against the parasite (the leak-lesion hypothesis) (2).We hypothesize that an increase in epithelial paracellular permeability resulting in the loss of parasites is a direct consequence of adaptive immunity. T. spiralis elicits a strong T helper 2 response resulting in intestinal goblet cell hyperplasia, eosinophilia, and a profound mucosal mastocytosis (3-5). Efficient parasite expulsion depends on CD4 ϩ T cells through control of the critical mast cell response (6). In the absence of intestinal mast cells the loss of parasites is markedly delayed (7). The mechanism by which mast cells induce parasite expulsion is unknown and is the focus of this study.Changes in epithelial paracellular permeability during the course of T. spiralis infection in mice and the role that the mast cell may play in inducing these changes were investigated. By depleting mast cells with anti-c-kit antibodies or by using IL-9 transgenic mice that overexpress mast cells (8), we present compelling evidence that mast cells are the key mediators of increased mucosal permeability. To understand further the action of mast cells on intestinal epithelium, we have infected mice deficient in mouse mast cell protease-1 (mMCP-1) that had been shown previously to delay parasite expulsion (9) and investigated whether this mast cell-specific proteinase is involved in increased epithelial perm...

show abstract

“…Expulsion of the parasites from the intestine is dependent on mast cells recruited to the mucosa in response to IL-4 and IL-9 (15)(16)(17). Furthermore, there are goblet cell hyperplasia and mucus hypersecretion that may provide mucosal protection for the host or create an inhospitable environment for the parasite (18). Moreover, distinctive changes in villus and crypt architecture occur that may also be an attempt by the host to drive out the parasite by diminishing the area available for habitation (18).…”

mentioning

confidence: 99%

“…Furthermore, there are goblet cell hyperplasia and mucus hypersecretion that may provide mucosal protection for the host or create an inhospitable environment for the parasite (18). Moreover, distinctive changes in villus and crypt architecture occur that may also be an attempt by the host to drive out the parasite by diminishing the area available for habitation (18). T cells are required for worm expulsion from the gut, but this is not IL-4 dependent, because mice genetically deficient for IL-4 can expel normally (19).…”

mentioning

confidence: 99%

Intraepithelial NK Cell-Derived IL-13 Induces Intestinal Pathology Associated with Nematode Infection

McDermott

Humphreys

Forman

et al. 2005

The Journal of Immunology

View full text Add to dashboard Cite

IL-13 is a Th2-derived cytokine associated with pathological changes in asthma and ulcerative colitis. Moreover, it plays a major role in the control of gut nematode infection and associated immunopathology. The current paradigm is that these effects are due to T cell-derived IL-13. We show in this study that an innate source of IL-13, the intraepithelial NK cell, is responsible for the disruption of intestinal tissue architecture and induction of goblet cell hyperplasia that characterizes infection with the intestinal helminth Trichinella spiralis. IL-13 or IL-4Rα (but not IL-4) null mice failed to induce intestinal pathology. Unexpectedly, SCID and athymic mice developed the same pathology found in immunocompetent mice following infection. Moreover, immunodeficient mice expressed IL-13 in the intestine, and abnormal mucosal pathology was reduced by in vivo administration of a soluble IL-13 antagonist. IL-13 expression was induced in non-T intraepithelial CD3− NK cells. Epithelial cells expressed the IL-13 signaling receptor, IL-13Rα1, and after infection, IL-4Rα. Furthermore, the soluble IL-13 decoy receptor IL-13Rα2, which regulates IL-13 responses, was also induced upon infection. These data provide the first evidence that intestinal tissue restructuring during helminth infection is an innate event dependent on IL-13 production by NK cells resident in the epithelium of the intestine.

show abstract

T lymphocyte dependent enteropathy in murine Trichinella spiralis infection

Cited by 68 publications

References 11 publications

The effect of the hookworm Ancylostoma ceylanicum on the mucosal architecture of the small intestine in hamsters

The effect of the hookworm Ancylostoma ceylanicum on the mucosal architecture of the small intestine in hamsters

Mast cells disrupt epithelial barrier function during enteric nematode infection

Intraepithelial NK Cell-Derived IL-13 Induces Intestinal Pathology Associated with Nematode Infection

Contact Info

Product

Resources

About