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Protective and pathogenic functions of T-cells are inseparable during the Helicobacter-host interaction


Mueller, A; Sayi, A; Hitzler, I (2009). Protective and pathogenic functions of T-cells are inseparable during the Helicobacter-host interaction. Discovery medicine, 8(41):68-73.

Abstract

Chronic infection with the bacterial pathogen Helicobacter pylori is closely linked to the development of gastric cancer. Experimental infection of the laboratory mouse strain C57Bl6 mimics the initiation and progression of the disease in humans. Using this model, we have identified a dual role for CD4+ IFN-gamma-secreting T-cells in the control of Helicobacter infection as well as in the induction of preneoplastic gastric pathology. High gastric expression of IFN-gamma was positively correlated with a low Helicobacter burden, and was essential for vaccine-induced protection; on the other hand, elevated levels of the cytokine also, either directly or indirectly, triggered the transformation of the normal gastric mucosa to atrophic, hyperplastic and metaplastic lesions. Based on similar patterns of gene expression changes induced by IFN-gamma in vivo and in cultured gastric epithelial cells, we hypothesize that IFN-gamma may act directly on epithelial cells to stimulate their hyperproliferation, and thus to predispose them to elevated mutation rates and an increased risk of malignant transformation.

Abstract

Chronic infection with the bacterial pathogen Helicobacter pylori is closely linked to the development of gastric cancer. Experimental infection of the laboratory mouse strain C57Bl6 mimics the initiation and progression of the disease in humans. Using this model, we have identified a dual role for CD4+ IFN-gamma-secreting T-cells in the control of Helicobacter infection as well as in the induction of preneoplastic gastric pathology. High gastric expression of IFN-gamma was positively correlated with a low Helicobacter burden, and was essential for vaccine-induced protection; on the other hand, elevated levels of the cytokine also, either directly or indirectly, triggered the transformation of the normal gastric mucosa to atrophic, hyperplastic and metaplastic lesions. Based on similar patterns of gene expression changes induced by IFN-gamma in vivo and in cultured gastric epithelial cells, we hypothesize that IFN-gamma may act directly on epithelial cells to stimulate their hyperproliferation, and thus to predispose them to elevated mutation rates and an increased risk of malignant transformation.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Molecular Cancer Research
07 Faculty of Science > Institute of Molecular Cancer Research

08 University Research Priority Programs > Systems Biology / Functional Genomics
Dewey Decimal Classification:570 Life sciences; biology
Language:English
Date:2009
Deposited On:15 Jan 2010 08:32
Last Modified:05 Apr 2016 13:45
Publisher:Solariz
ISSN:1539-6509
Official URL:http://www.discoverymedicine.com/Anne-Mueller/2009/09/23/protective-and-pathogenic-functions-of-t-cells-are-inseparable-during-the-helicobacter-host-interaction/
PubMed ID:19788871

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