Lack of gastritis and of an adaptive immune response in interferon regulatory factor-1-deficient mice infected with Helicobacter pylori.
To study the role of T cell responses in Helicobacter pylori gastritis, C57BL/6 wild-type and interferon regulatory factor-1-deficient (IRF-1(-/-)) mice were infected with the mouse-adapted H. pylori Sydney strain. Mice lacking the transcription factor IRF-1 are defective in Th1 development and are therefore biased to mount a Th2-type response. After 4 months of infection, C57BL/6 mice developed severe gastritis and atrophy and mounted a Th1-type response towards H. pylori. The Th1 response was abrogated in IRF-1(-/-) mice. This defective Th1 response was associated with the total lack of gastritis and atrophy in IRF-1(-/-) mice despite severe colonization with H. pylori. In addition, IRF-1(-/-) mice did also not develop a Th2 reaction, since they failed to generate H. pylori-specific antibodies and to produce IL-4 in response to H. pylori antigens in vitro. Thus, the transcription factor IRF-1 is necessary for the development of gastritis and atrophy in H. pylori-infected wild-type mice, suggesting a role of Th1 cells in the pathogenesis of H. pylori-associated diseases.
Sommer
F
F
Institut für Klinische Mikrobiologie, Immunologie und Hygiene, University of Erlangen, Erlangen, Germany. sommerf@mailer.uni-marburg.de
Faller
G
G
Röllinghoff
M
M
Kirchner
T
T
Mak
T W
TW
Lohoff
M
M
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D004268:DNA-Binding Proteins / Q000502:physiology*; D005260:Female; D005756:Gastritis / Q000209:etiology* / Q000382:microbiology; D016481:Helicobacter Infections / Q000276:immunology*; D016480:Helicobacter pylori / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood; D050856:Interferon Regulatory Factor-1; D051379:Mice; D008810:Mice, Inbred C57BL; D010750:Phosphoproteins / Q000502:physiology*; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D000907:Antibodies, Bacterial; D004268:DNA-Binding Proteins; D007074:Immunoglobulin G; D050856:Interferon Regulatory Factor-1; C494258:Irf1 protein, mouse; D010750:Phosphoproteins