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The CD4+ T cell-mediated IFN-gamma response to Helicobacter infection is essential for clearance and determines gastric cancer risk

Sayi, A; Kohler, E; Hitzler, I; Arnold, I; Schwendener, R; Rehrauer, H; Müller, Anne (2009). The CD4+ T cell-mediated IFN-gamma response to Helicobacter infection is essential for clearance and determines gastric cancer risk. Journal of Immunology, 182(11):7085-7101.

Abstract

Chronic infection with the bacterial pathogen Helicobacter pylori is a risk factor for the development of gastric cancer, yet remains asymptomatic in the majority of individuals. We report here that the C57BL/6 mouse model of experimental infection with the closely related Helicobacter felis recapitulates this wide range in host susceptibility. Although the majority of infected animals develop premalignant lesions such as gastric atrophy, compensatory epithelial hyperplasia, and intestinal metaplasia, a subset of mice is completely protected from preneoplasia. Protection is associated with a failure to mount an IFN-gamma response to the infection and with a concomitant high Helicobacter burden. Using a vaccine model as well as primary infection and adoptive transfer models, we demonstrate that IFN-gamma, secreted predominantly by CD4(+)CD25(-) effector T(H) cells, is essential for Helicobacter clearance, but at the same time mediates the formation of preneoplastic lesions. We further provide evidence that IFN-gamma triggers a common transcriptional program in murine gastric epithelial cells in vitro and in vivo and induces their preferential transformation to the hyperplastic phenotype. In summary, our data suggest a dual role for IFN-gamma in Helicobacter pathogenesis that could be the basis for the differential susceptibility to H. pylori-induced gastric pathology in the human population.

Additional indexing

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

08 Research Priority Programs > Systems Biology / Functional Genomics
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Scopus Subject Areas:Health Sciences > Immunology and Allergy
Life Sciences > Immunology
Language:English
Date:2009
Deposited On:08 Jun 2009 11:46
Last Modified:02 Nov 2024 02:41
Publisher:American Association of Immunologists
ISSN:0022-1767
OA Status:Closed
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.4049/jimmunol.0803293
PubMed ID:19454706

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