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, Gene-Deficient Mice1
Departments of
*
Medicine,
Pathology, and
Comparative Medicine, University of Alabama, Birmingham, AL 35294;
§
Immunobiological Research Institute Siena, Chiron Biocine SpA, Siena, Italy; and
¶
Veterans Affairs Medical Center, Birmingham, AL 35294
To elucidate the pathogenesis of Helicobacter
pylori-associated gastritis, we studied immune responses of
C57BL/6J wild-type (WT), SCID, and gene deficient
(IFN-
-/- and
IL-4-/-) mice following infection with a
pathogenic isolate of H. pylori (SPM326). During early
infection in WT mice, mononuclear and polymorphonuclear cells
accumulated in the gastric lamina propria, and the numbers of cells in
the inflamed mucosa expressing IFN-, but not IL-4, mRNA rose
significantly (p < 0.005), consistent with a local
Th1 response. Splenic T cells from the same infected WT mice produced
high levels of IFN-, no detectable IL-4, and low amounts of IL-10
following in vitro H. pylori urease stimulation,
reflecting a systemic Th1 response. Infected C57BL/6J SCID mice did not
develop gastric inflammation despite colonization by many bacteria.
Infected C57BL/10J and BALB/c mice also did not develop gastric
inflammation and displayed a mixed Th1/Th2 splenic cytokine profile.
These data imply a major role for the Th1 cytokine IFN- in H.
pylori-associated gastric inflammation in C57BL/6J mice.
Compared with WT animals, infected IL-4-/-
animals had more severe gastritis and higher levels of IFN-
production by urease-stimulated splenocytes (p <
0.01), whereas IFN--/- mice exhibited no
gastric inflammation and higher levels of IL-4 production by stimulated
splenocytes. These findings establish C57BL/6J mice as an important
model for H. pylori infection and demonstrate that
up-regulated production of IFN-, in the absence of the opposing
effects of IL-4 (and possibly IL-10), plays a pivotal role in promoting
H. pylori-induced mucosal
inflammation.
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P. Voland, N. Hafsi, M. Zeitner, S. Laforsch, H. Wagner, and C. Prinz Antigenic Properties of HpaA and Omp18, Two Outer Membrane Proteins of Helicobacter pylori Infect. Immun., July 1, 2003; 71(7): 3837 - 3843. [Abstract] [Full Text] [PDF]
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C. A. Garhart, J. G. Nedrud, F. P. Heinzel, N. E. Sigmund, and S. J. Czinn Vaccine-Induced Protection against Helicobacter pylori in Mice Lacking Both Antibodies and Interleukin-4 Infect. Immun., June 1, 2003; 71(6): 3628 - 3633. [Abstract] [Full Text] [PDF]
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C. A. Garhart, F. P. Heinzel, S. J. Czinn, and J. G. Nedrud Vaccine-Induced Reduction of Helicobacter pylori Colonization in Mice Is Interleukin-12 Dependent but Gamma Interferon and Inducible Nitric Oxide Synthase Independent Infect. Immun., February 1, 2003; 71(2): 910 - 921. [Abstract] [Full Text] [PDF]
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U. Thalmaier, N. Lehn, K. Pfeffer, M. Stolte, M. Vieth, and W. Schneider-Brachert Role of Tumor Necrosis Factor Alpha in Helicobacter pylori Gastritis in Tumor Necrosis Factor Receptor 1-Deficient Mice Infect. Immun., June 1, 2002; 70(6): 3149 - 3155. [Abstract] [Full Text] [PDF]
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M. Obonyo, D. G. Guiney, J. Harwood, J. Fierer, and S. P. Cole Role of Gamma Interferon in Helicobacter pylori Induction of Inflammatory Mediators during Murine Infection Infect. Immun., June 1, 2002; 70(6): 3295 - 3299. [Abstract] [Full Text] [PDF]
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R. Rad, M. Gerhard, R. Lang, M. Schoniger, T. Rosch, W. Schepp, I. Becker, H. Wagner, and C. Prinz The Helicobacter pylori Blood Group Antigen-Binding Adhesin Facilitates Bacterial Colonization and Augments a Nonspecific Immune Response J. Immunol., March 15, 2002; 168(6): 3033 - 3041. [Abstract] [Full Text] [PDF]
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K. A. Eaton, M. Mefford, and T. Thevenot The Role of T Cell Subsets and Cytokines in the Pathogenesis of Helicobacter pylori Gastritis in Mice J. Immunol., June 15, 2001; 166(12): 7456 - 7461. [Abstract] [Full Text] [PDF]
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B. Lucas, D. Bumann, A. Walduck, J. Koesling, L. Develioglu, T. F. Meyer, and T. Aebischer Adoptive Transfer of CD4+ T Cells Specific for Subunit A of Helicobacter pylori Urease Reduces H. pylori Stomach Colonization in Mice in the Absence of Interleukin-4 (IL-4)/IL-13 Receptor Signaling Infect. Immun., March 1, 2001; 69(3): 1714 - 1721. [Abstract] [Full Text] [PDF]
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T T MACDONALD The worm turns on Helicobacter pylori Gut, January 1, 2001; 48(1): 10 - 11. [Full Text] [PDF]
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