Trichuris muris: host intestinal epithelial cell hyperproliferation during chronic infection is regulated by interferon-gamma.

2.50
Hdl Handle:
http://hdl.handle.net/10541/91346
Title:
Trichuris muris: host intestinal epithelial cell hyperproliferation during chronic infection is regulated by interferon-gamma.
Authors:
Artis, David; Potten, Christopher S; Else, Kathryn J; Finkelman, Fred D; Grencis, Richard K
Abstract:
Chronic infection with the intestinal nematode Trichuris muris is associated with an inappropriate type 1 cytokine response (production of predominantly IFN-gamma), whereas resistance to infection requires the induction of a protective type 2 response with the production of interleukin (IL)-4, IL-5, IL-9, and IL-13. T. muris inhabits an intracellular niche within murine intestinal epithelial cells of the caecum and in common with other intestinal helminth infections is associated with gross morphological changes in gut architecture. The purpose of this study was to characterise cytokine production during chronic infection in AKR and severe-combined-immunodeficient (SCID) mice and investigate what effect the anti-parasite response had on epithelial cell proliferation and so regulation of intestinal pathology. Pulse labeling with tritiated thymidine is employed to generate a sensitive cell position-linked proliferation index of the intestinal epithelium at various times postinfection. Infection in AKR mice is characterized by a marked elevation in antigen specific IFN-gamma production from restimulated mesenteric lymph node cells and a significant increase in proliferation of pluripotent epithelial stem cells and transit cells within the crypts. Similarly, elevated IFN-gamma production was observed in the mesenteric lymph nodes and intestinal mucosa of infected SCID mice, with epithelial cell hyperproliferation and the development of crypt hyperplasia in the caecum. Critically, in vivo depletion of IFN-gamma during infection in SCID mice resulted in no significant increase in epithelial cell proliferation and effectively precluded the development of crypt hyperplasia without altering infection outcome. Taken together, the data provides the first detailed cell position linked analysis of epithelial dysregulation during chronic T. muris infection and identifies a critical role for IFN-gamma, either directly or indirectly, in regulation of epithelial cell proliferation during the chronic intestinal inflammation associated with infection.
Affiliation:
Immunology Research Group, School of Biological Sciences, University of Manchester, 3.239 Stopford Building, Manchester, M13 9PT, United Kingdom.
Citation:
Trichuris muris: host intestinal epithelial cell hyperproliferation during chronic infection is regulated by interferon-gamma. 1999, 92 (2):144-53 Exp. Parasitol.
Journal:
Experimental Parasitology
Issue Date:
Jun-1999
URI:
http://hdl.handle.net/10541/91346
DOI:
10.1006/expr.1999.4407
PubMed ID:
10366539
Type:
Article
Language:
en
ISSN:
0014-4894
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorArtis, Daviden
dc.contributor.authorPotten, Christopher Sen
dc.contributor.authorElse, Kathryn Jen
dc.contributor.authorFinkelman, Fred Den
dc.contributor.authorGrencis, Richard Ken
dc.date.accessioned2010-02-08T11:16:32Z-
dc.date.available2010-02-08T11:16:32Z-
dc.date.issued1999-06-
dc.identifier.citationTrichuris muris: host intestinal epithelial cell hyperproliferation during chronic infection is regulated by interferon-gamma. 1999, 92 (2):144-53 Exp. Parasitol.en
dc.identifier.issn0014-4894-
dc.identifier.pmid10366539-
dc.identifier.doi10.1006/expr.1999.4407-
dc.identifier.urihttp://hdl.handle.net/10541/91346-
dc.description.abstractChronic infection with the intestinal nematode Trichuris muris is associated with an inappropriate type 1 cytokine response (production of predominantly IFN-gamma), whereas resistance to infection requires the induction of a protective type 2 response with the production of interleukin (IL)-4, IL-5, IL-9, and IL-13. T. muris inhabits an intracellular niche within murine intestinal epithelial cells of the caecum and in common with other intestinal helminth infections is associated with gross morphological changes in gut architecture. The purpose of this study was to characterise cytokine production during chronic infection in AKR and severe-combined-immunodeficient (SCID) mice and investigate what effect the anti-parasite response had on epithelial cell proliferation and so regulation of intestinal pathology. Pulse labeling with tritiated thymidine is employed to generate a sensitive cell position-linked proliferation index of the intestinal epithelium at various times postinfection. Infection in AKR mice is characterized by a marked elevation in antigen specific IFN-gamma production from restimulated mesenteric lymph node cells and a significant increase in proliferation of pluripotent epithelial stem cells and transit cells within the crypts. Similarly, elevated IFN-gamma production was observed in the mesenteric lymph nodes and intestinal mucosa of infected SCID mice, with epithelial cell hyperproliferation and the development of crypt hyperplasia in the caecum. Critically, in vivo depletion of IFN-gamma during infection in SCID mice resulted in no significant increase in epithelial cell proliferation and effectively precluded the development of crypt hyperplasia without altering infection outcome. Taken together, the data provides the first detailed cell position linked analysis of epithelial dysregulation during chronic T. muris infection and identifies a critical role for IFN-gamma, either directly or indirectly, in regulation of epithelial cell proliferation during the chronic intestinal inflammation associated with infection.en
dc.language.isoenen
dc.subject.meshAnimals-
dc.subject.meshAntibodies, Monoclonal-
dc.subject.meshCecum-
dc.subject.meshCell Division-
dc.subject.meshChronic Disease-
dc.subject.meshEpithelial Cells-
dc.subject.meshFemale-
dc.subject.meshInterferon-gamma-
dc.subject.meshIntestinal Diseases, Parasitic-
dc.subject.meshIntestinal Mucosa-
dc.subject.meshIntestines-
dc.subject.meshKinetics-
dc.subject.meshLymph Nodes-
dc.subject.meshMale-
dc.subject.meshMice-
dc.subject.meshMice, Inbred AKR-
dc.subject.meshMice, SCID-
dc.subject.meshRNA, Messenger-
dc.subject.meshThymidine-
dc.subject.meshTrichuriasis-
dc.subject.meshTrichuris-
dc.subject.meshTritium-
dc.titleTrichuris muris: host intestinal epithelial cell hyperproliferation during chronic infection is regulated by interferon-gamma.en
dc.typeArticleen
dc.contributor.departmentImmunology Research Group, School of Biological Sciences, University of Manchester, 3.239 Stopford Building, Manchester, M13 9PT, United Kingdom.en
dc.identifier.journalExperimental Parasitologyen
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