Helicobacter pylori-induced Th17 responses modulate Th1 cell responses, benefit bacterial growth, and contribute to pathology in mice.
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.
Shi
Yun
Y
Department of Clinical Microbiology and Immunology, Third Military Medical University, Chongqing 400038, China.
Liu
Xiao-Fei
XF
Zhuang
Yuan
Y
Zhang
Jin-Yu
JY
Liu
Tao
T
Yin
Zhinan
Z
Wu
Chao
C
Mao
Xu-Hu
XH
Jia
Ke-Ran
KR
Wang
Feng-Jun
FJ
Guo
Hong
H
Flavell
Richard A
RA
Zhao
Zhuo
Z
Liu
Kai-Yun
KY
Xiao
Bin
B
Guo
Ying
Y
Zhang
Wei-Jun
WJ
Zhou
Wei-Ying
WY
Guo
Gang
G
Zou
Quan-Ming
QM
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
D020381:Interleukin-17; D053759:Interleukin-23; D018664:Interleukin-12; D007371:Interferon-gamma