Mucosal T cells regulate Paneth and intermediate cell numbers in the small intestine of <i>T. spiralis</i>-infected mice

Kamal, M; Wakelin, D.; Ouellette, André J.; Smith, Adrian L.; Podolsky, Daniel K.; Mahida, Yashwant R.

doi:10.1046/j.1365-2249.2001.01589.x

Cited by 78 publications

(93 citation statements)

References 36 publications

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“…Other antinematode effector mechanisms modulated by IL-9 or IL-13 include increased epithelial cell turnover acting like an epithelial escalator to expel Trichuris parasites (11) and jejunal muscle hypercontractility (37). Paneth cell hyperplasia has also been reported during T. spiralis infection, and this process seemed T cell-dependent (13), but the role of IL-9 and IL-13 in this process had not been described so far. The up-regulation of Paneth cell-derived antimicrobial products, including cryptdins, Ang4, and PLA2g2a might therefore directly contribute to the anti-parasite response.…”

Section: Discussionmentioning

confidence: 99%

“…Although the actual effector mechanisms by which TH2-polarized immune responses allow for parasite expulsion are not completely elucidated, epithelial cells seem to be actively involved in this process, for instance as a result of accelerated cell turnover (11). Paneth cell hyperplasia is also associated with nematode infections (12,13). Although there is no evidence that intestinal epithelial cells respond to IL-9, the similarities between the lung and intestinal mucosae, as well as the fact that IL-9-induced mastocytosis seemed mainly restricted to these tissues, prompted us to investigate the potential activity of IL-9 on colonic epithelial cells in vivo.…”

mentioning

confidence: 99%

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IL-9 Promotes IL-13-Dependent Paneth Cell Hyperplasia and Up-Regulation of Innate Immunity Mediators in Intestinal Mucosa

Steenwinckel

Louahed²,

Lemaire³

et al. 2009

The Journal of Immunology

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IL-9 contributes to lung inflammatory processes such as asthma, by promoting mast cell differentiation, B cell activation, eosinophilia, and mucus production by lung epithelial cells. The observation that IL-9 overexpressing mice show increased mast cell numbers in the intestinal mucosa suggests that this cytokine might also play a role in intestinal inflammation. In colons from IL-9 transgenic mice, the expression of Muc2, a major intestinal mucin gene, was up-regulated, together with that of CLCA3 chloride channel and resistin like α, which are goblet cell-associated genes. Additional IL-9 up-regulated genes were identified and included innate immunity genes such as angiogenin 4 and the PLA2g2a phospholipase A2, which are typical Paneth cell markers. Histochemical staining of Paneth cells by phloxine/tartrazine showed that IL-9 induces Paneth cell hyperplasia in Lieberkühn glands of the small intestine, and in the colonic mucosa, where this cell type is normally absent. Expression of Paneth cell markers, including angiogenin 4, PLA2g2a, and cryptdins, was induced in the colon of wild-type mice after two to four daily administrations of IL-9. By crossing IL-9 transgenic mice with IL-13−/− mice, or by injecting IL-9 into IL-4R−/− mice, we showed that IL-13 was required for the up-regulation of these Paneth cell-specific genes by IL-9. Taken together, our data indicate that Paneth cell hyperplasia and expression of their various antimicrobial products contribute to the immune response driven by TH2 cytokines, such as IL-9 and IL-13 in the intestinal mucosa.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

IL-9 Promotes IL-13-Dependent Paneth Cell Hyperplasia and Up-Regulation of Innate Immunity Mediators in Intestinal Mucosa

Steenwinckel

Louahed²,

Lemaire³

et al. 2009

The Journal of Immunology

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“…The rise in mast cell counts is consistent with earlier reports (Garside & Behnke, 1989;Behnke, 1991;Behnke et al, 1997), as is that for goblet cells (Garside et al, 1990), but to the best of our knowledge, Paneth cells have not been assessed previously in this system. Counter-intuitively, given data from intestinal nematode-mouse models (Kamal et al, 2001), the intestinal response was characterized by a fall in Paneth cell numbers. All these changes in cell populations in the mucosa were dependent on the presence of adult worms, and normal levels were restored soon after worms were removed by treatment, although some cell types returned to baseline more quickly than others (e.g.…”

Section: Discussionmentioning

confidence: 99%

“…Paneth cells, located in the bases of the crypts of Lieberkuhn, have an important role in antimicrobial mucosal defence. In mice infected with T. spiralis and other intestinal nematodes their numbers increase within a few days of infection, and then decline once the worms have been eliminated (Kamal et al, 2001(Kamal et al, , 2002Elphick & Mahida, 2005). Collectively, these cellular changes are accompanied by gross changes of the mucosal architecture, reflected in a reduction of the size of villi and hyperplasia in the crypts (Garside et al, 1992;Lawrence et al, 2000) Hookworm infections, which give rise to chronic infections in humans and animals (Behnke, 1987) are known also to stimulate intestinal inflammatory responses, probably the earliest evidence for this going back to Whipple (1909).…”

Section: Introductionmentioning

confidence: 99%

The mucosal cellular response to infection withAncylostoma ceylanicum

2008

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Although hookworms are known to stimulate inflammatory responses in the intestinal mucosa of their hosts, there is little quantitative data on this aspect of infection. Here we report the results of experiments conducted in hamsters infected with Ancylostoma ceylanicum. Infection resulted in a marked increase in goblet cells in the intestinal mucosa, which was dependent on the number of adult worms present and was sustained as long as worms persisted (over 63 days) but returned to baseline levels within 7 days of the removal of worms by treatment with ivermectin. Increased mast cell responses were also recorded. Levels were again dependent on the intensity of worm burdens and lasted as long as 63 days after infection. When worms were eliminated, mast cell numbers took over 2 weeks to return to normal. Paneth cell numbers fell soon after infection, the degree of reduction being dependent on the worm burden. After clearance of worms, Paneth cell numbers returned to normal within a week, but then rebounded and numbers rose to higher levels than those in control naïve animals. The time course of the response was similar whether animals experienced a chronic low-intensity infection without loss of worms or a higher intensity infection during the course of which worm burdens were gradually reduced. Clearly, A. ceylanicum was able to induce a marked inflammatory response in its host's intestine which was sustained for over 9 weeks after infection, and which hamsters appeared able to tolerate well. Our data draw attention to the resilience of hookworms which, unlike many other nematodes, are able to survive for many weeks in a highly inflamed intestinal tract.

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“…Our data demonstrate that they also appear following infection with T. muris and suggest that IL-4 and IL-10 may contribute to Paneth cell development. Baseline levels of Paneth cells as well as goblet cells are increased in the small intestine following infection with T. spiralis (54), although these cells are not required for worm expulsion from the small intestine (55). The induction of these cells in the cecum and colon, however, may act as a barrier to prevent parasites and bacteria from maintaining their attachment to the mucosal surface.…”

Section: Discussionmentioning

confidence: 99%

IL-10 Is Critical for Host Resistance and Survival During Gastrointestinal Helminth Infection

Schopf

Hoffmann

Cheever

et al. 2002

The Journal of Immunology

193

168

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Resistance to many intestinal nematodes is dependent on the induction of polarized type 2 cytokine responses, whereas type 1 responses can exacerbate these infections. The contributions of IL-4 and IL-13 to the development of resistance have been well described for a variety of intestinal parasites; however, the role of IL-10 has not been previously investigated. In this study we infected IL-10-, IL-10/IL-4-, IL-10/IL-12-, IL-4-, and IL-12-deficient mice with Trichuris muris to determine whether IL-10 contributes to the development of immunity. Interestingly, T. muris-infected IL-10-, IL-4-, and IL-10/IL-4-deficient mice failed to expel the parasite, and animals deficient in IL-10 displayed marked morbidity and mortality. In contrast, double IL-10/IL-12-deficient mice were completely resistant and mounted a highly polarized type 2 cytokine response, demonstrating that the increased susceptibility of IL-10-deficient mice was dependent on IL-12. Further study suggested that the susceptibility of IL-10- and IL-10/IL-4-deficient mice was probably attributable to a marked increase in type 1 cytokine production in those animals. The mortality observed in T. muris-infected IL-10- and IL-10/IL-4-deficient mice correlated with increased inflammation, loss of Paneth cells, and absence of mucus in the cecum. Interestingly, survival was enhanced in T. muris-infected IL-10/IL-4-deficient mice if a broad spectrum antibiotic was administered, suggesting that an outgrowth of opportunistic bacteria was contributing to the high degree of morbidity and mortality. Overall, these studies reveal a critical role for IL-10 in the polarization of Th2 responses, development of resistance during T. muris infection, and maintenance of barrier function in the colon.

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Mucosal T cells regulate Paneth and intermediate cell numbers in the small intestine of T. spiralis-infected mice

Cited by 78 publications

References 36 publications

IL-9 Promotes IL-13-Dependent Paneth Cell Hyperplasia and Up-Regulation of Innate Immunity Mediators in Intestinal Mucosa

IL-9 Promotes IL-13-Dependent Paneth Cell Hyperplasia and Up-Regulation of Innate Immunity Mediators in Intestinal Mucosa

The mucosal cellular response to infection withAncylostoma ceylanicum

IL-10 Is Critical for Host Resistance and Survival During Gastrointestinal Helminth Infection

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