Paneth cells: their role in innate immunity and inflammatory disease

Elphick, David; Mahida, Yashwant R.

doi:10.1136/gut.2005.068601

Cited by 157 publications

(123 citation statements)

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“…Hamsters are known to have Paneth cells with granules that are similar to those in other rodents and mammals, at least at the electron microscope level (Satoh et al, 1990). The biology of these cell has been reviewed recently (Elphick & Mahida, 2005) and their numbers in crypts are believed to be controlled by a unique nonthymus-dependent mucosal T-cell population (Kamal et al, 2001). Hookworms are known to secrete a range of bioactive molecules, some of which are believed to play a role in their survival strategy in the face of the host immune system (Loukas & Prociv, 2001;Ghosh et al, 2006).…”

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%

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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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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The mucosal cellular response to infection withAncylostoma ceylanicum

2008

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“…Secretion of antimicrobial peptides by Paneth cells is an important protective mechanism by which intestinal immune homeostasis is established 28,29 , and defects in Paneth cell function have been described in IBD patients 30,31 35 . In addition, mice defective in ER stress signalling or autophagy, such as XBP1 IEC-KO mice 36 and hypomorphic ATG16L1 mice 37 , respectively, display Paneth cell abnormalities.…”

Section: Discussionmentioning

confidence: 99%

A20 controls intestinal homeostasis through cell-specific activities

et al. 2014

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The transcription factor NF-kB is indispensable for intestinal immune homeostasis, but contributes to chronic inflammation and inflammatory bowel disease (IBD). A20, an inhibitor of both NF-kB and apoptotic signalling, was identified as a susceptibility gene for multiple inflammatory diseases, including IBD. Despite absence of spontaneous intestinal inflammation in intestinal epithelial cell (IEC) specific A20 knockout mice, we found additional myeloid-specific A20 deletion to synergistically drive intestinal pathology through cell-specific mechanisms. A20 ensures intestinal barrier stability by preventing cytokine-induced IEC apoptosis, while A20 prevents excessive cytokine production in myeloid cells. Combining IEC and myeloid A20 deletion induces ileitis and severe colitis, characterized by IEC apoptosis, Paneth and goblet cell loss, epithelial hyperproliferation and intestinal microbiota dysbiosis. Continuous epithelial cell death and regeneration in an inflammatory environment sensitizes cells for neoplastic transformation and the development of colorectal tumours in aged mice.

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“…TLRs which are the major pattern recognition receptors of innate immunity, by recognizing pathogen associated molecular patterns, activating the innate immune system to produce proinflammatory cytokines and defensins resist damage caused by pathogens (Elphick & Mahida, 2005). NOD2 is a new pattern recognition molecule, participating in the antibacterial and anti-invasion effect of host cell by the identification of intracellular bacterial components.…”

Section: Paneth Cell Defensins Regulate Innate Immune Responses By Nomentioning

confidence: 99%