title: Helicobacter pylori-induced Th17 responses modulate Th1 cell responses, benefit bacterial growth, and contribute to pathology in mice.
abstract: CD4(+) T cell responses are critical for the pathogenesis of Helicobacter pylori infection. The present study evaluated the role of the Th17 subset in H. pylori infection. H. pylori infection induced significant expression of IL-17 and IFN-gamma in mouse gastric tissue. IL-23 and IL-12 were increased in the gastric tissue and in H. pylori-stimulated macrophages. Cell responses were examined by intracellular staining for IFN-gamma, IL-4, and IL-17. Mice infected with H. pylori developed a mixed Th17/Th1 response; Th17 responses preceded Th1 responses. Treatment of mice with an anti-IL-17 Ab but not a control Ab significantly reduced the H. pylori burden and inflammation in the stomach. H. pylori colonization and gastric inflammation were also lower in IL-17(-/-) mice. Furthermore, administration of recombinant adenovirus encoding mouse IL-17 increased both H. pylori load and inflammation. Further analysis showed that the Th1 cell responses to H. pylori were downregulated when IL-17 is deficient. These results together suggest that H. pylori infection induces a mixed Th17/Th1 cell response and the Th17/IL-17 pathway modulates Th1 cell responses and contributes to pathology.
authors.affiliation: Department of Clinical Microbiology and Immunology, Third Military Medical University, Chongqing 400038, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Shi
authors.forename: Xiao-Fei
authors.initials: XF
authors.lastname: Liu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhuang
authors.forename: Jin-Yu
authors.initials: JY
authors.lastname: Zhang
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.forename: Zhinan
authors.initials: Z
authors.lastname: Yin
authors.forename: Chao
authors.initials: C
authors.lastname: Wu
authors.forename: Xu-Hu
authors.initials: XH
authors.lastname: Mao
authors.forename: Ke-Ran
authors.initials: KR
authors.lastname: Jia
authors.forename: Feng-Jun
authors.initials: FJ
authors.lastname: Wang
authors.forename: Hong
authors.initials: H
authors.lastname: Guo
authors.forename: Richard A
authors.initials: RA
authors.lastname: Flavell
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Zhao
authors.forename: Kai-Yun
authors.initials: KY
authors.lastname: Liu
authors.forename: Bin
authors.initials: B
authors.lastname: Xiao
authors.forename: Ying
authors.initials: Y
authors.lastname: Guo
authors.forename: Wei-Jun
authors.initials: WJ
authors.lastname: Zhang
authors.forename: Wei-Ying
authors.initials: WY
authors.lastname: Zhou
authors.forename: Gang
authors.initials: G
authors.lastname: Guo
authors.forename: Quan-Ming
authors.initials: QM
authors.lastname: Zou
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D005260:Female; D016481:Helicobacter Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology*; D016480:Helicobacter pylori / Q000254:growth & development / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D020381:Interleukin-17 / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D053759:Interleukin-23 / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
chemical_list: D020381:Interleukin-17; D053759:Interleukin-23; D018664:Interleukin-12; D007371:Interferon-gamma