Regulation of Gastric B Cell Recruitment Is Dependent on IL-17 Receptor A Signaling in a Model of Chronic Bacterial Infection

被引:51
作者
Algood, Holly M. Scott [1 ,2 ]
Allen, Shannon Sedberry
Washington, Mary K.
Peek, Richard M., Jr. [1 ,3 ]
Miller, Geraldine G.
Cover, Timothy L. [1 ,4 ]
机构
[1] Vet Affairs Tennessee Valley Healthcare Syst, Nashville, TN 37212 USA
[2] Vanderbilt Univ, Sch Med, Div Infect Dis, Med Ctr N A2200,Dept Pathol, Nashville, TN 37232 USA
[3] Vanderbilt Univ, Sch Med, Dept Canc Biol, Nashville, TN 37232 USA
[4] Vanderbilt Univ, Sch Med, Dept Microbiol & Immunol, Nashville, TN 37232 USA
基金
美国国家卫生研究院;
关键词
HELICOBACTER-PYLORI INFECTION; DELTA-T-CELLS; COLONY-STIMULATING FACTOR; HOST-DEFENSE; INFLAMMATORY RESPONSES; NEUTROPHIL RECRUITMENT; PNEUMONIAE INFECTION; SECRETING CELLS; IMMUNE-RESPONSE; MOUSE MODEL;
D O I
10.4049/jimmunol.0901206
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Th17-driven immune responses contribute to the pathogenesis of many chronic inflammatory diseases. In this study, we investigated the role of IL-17 signaling in chronic gastric inflammation induced by Helicobacter pylori, a Gram-negative bacterium that persistently colonizes the human stomach. Wild-type C57BL/6 mice and mice lacking IL-17RA (IL-17RA(-/-)) were orogastrically infected with H. pylori. Differences in bacterial colonization density and gastric inflammation were not apparent at 1 mo postinfection, but by 3 mo postinfection, H. pylori colonization density was higher and mononuclear gastric inflammation more severe in infected IL-17RA(-/-) mice than in infected wild-type mice. A striking feature was a marked increase in gastric B cells, plasma cells, and lymphoid follicles, along with enhanced H. pylori-specific serum Ab responses, in infected IL-17RA(-/-) mice. Fewer gastric neutrophils and lower levels of neutrophil-recruiting chemokines were detected in infected IL-17RA(-/-) mice than in infected wild-type mice. Gastric IL-17a and IL-21 transcript levels were significantly higher in infected IL-17RA(-/-) mice than in infected wild-type mice or uninfected mice, which suggested that a negative feedback loop was impaired in the IL-17RA(-/-) mice. These results underscore an important role of IL-17RA signaling in regulating B cell recruitment. In contrast to many chronic inflammatory diseases in which IL-17RA signaling promotes an inflammatory response, IL-17RA signaling down-regulates the chronic mononuclear inflammation elicited by H. pylori infection. The Journal of Immunology, 2009, 183: 5837-5846.
引用
收藏
页码:5837 / 5846
页数:10
相关论文
共 58 条
[1]   Helicobacter pylori-specific antibodies impair the development of gastritis, facilitate bacterial colonization, and counteract resistance against infection [J].
Akhiani, AA ;
Schön, K ;
Franzén, LE ;
Pappo, J ;
Lycke, N .
JOURNAL OF IMMUNOLOGY, 2004, 172 (08) :5024-5033
[2]   Host response to Helicobacter pylori infection before initiation of the adaptive immune response [J].
Algood, Holly M. Scott ;
Gallo-Romero, Judith ;
Wilson, Keith T. ;
Peek, Richard M., Jr. ;
Cover, Timothy L. .
FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY, 2007, 51 (03) :577-586
[3]   Helicobacter pylori persistence:: An overview of interactions between H-pylori and host immune defenses [J].
Algood, Holly M. Scott ;
Cover, Timothy L. .
CLINICAL MICROBIOLOGY REVIEWS, 2006, 19 (04) :597-+
[4]   Host-bacterial interactions in Helicobacter pylori infection [J].
Amieva, Manuel R. ;
El-Omar, Emad M. .
GASTROENTEROLOGY, 2008, 134 (01) :306-323
[5]   SURVIVAL AND ULTRASTRUCTURAL-CHANGES OF HELICOBACTER-PYLORI AFTER PHAGOCYTOSIS BY HUMAN POLYMORPHONUCLEAR LEUKOCYTES AND MONOCYTES [J].
ANDERSEN, LP ;
BLOM, J ;
NIELSEN, H .
APMIS, 1993, 101 (01) :61-72
[6]   Lymphocytes in the human gastric mucosa during Helicobacter pylori have a T helper cell 1 phenotype [J].
Bamford, KB ;
Fan, XJ ;
Crowe, SE ;
Leary, JF ;
Gourley, WK ;
Luthra, GK ;
Brooks, EG ;
Graham, DY ;
Reyes, VE ;
Ernst, PB .
GASTROENTEROLOGY, 1998, 114 (03) :482-492
[7]   Induction and effector functions of TH17 cells [J].
Bettelli, Estelle ;
Korn, Thomas ;
Oukka, Mohamed ;
Kuchroo, Vijay K. .
NATURE, 2008, 453 (7198) :1051-1057
[8]   Pathology of mouse models of intestinal cancer: Consensus report and recommendations [J].
Boivin, GP ;
Washington, K ;
Yang, K ;
Ward, JM ;
Pretlow, TP ;
Russell, R ;
Besselsen, DG ;
Godfrey, VL ;
Doetschman, T ;
Dove, WF ;
Pitot, HC ;
Halberg, RB ;
Itzkowitz, SH ;
Groden, J ;
Coffey, RJ .
GASTROENTEROLOGY, 2003, 124 (03) :762-777
[9]   IL-23-mediated regulation of IL-17 production in Helicobacter pylori-infected gastric mucosa [J].
Caruso, Roberta ;
Fina, Daniele ;
Paoluzi, Omero Alessandro ;
Blanco, Giovanna Del Vecchio ;
Stolfi, Carmine ;
Rizzo, Angelarnaria ;
Caprioli, Flavio ;
Sarra, Massimiliano ;
Andrei, Fabio ;
Fantini, Massimo Claudio ;
MacDonald, Thomas T. ;
Pallone, Francesco ;
Monteleone, Giovanni .
EUROPEAN JOURNAL OF IMMUNOLOGY, 2008, 38 (02) :470-478
[10]   Pertussis toxin by inducing IL-6 promotes the generation of IL-17-producing CD4 cells [J].
Chen, Xin ;
Howard, O. M. Zack ;
Oppenheim, Joost J. .
JOURNAL OF IMMUNOLOGY, 2007, 178 (10) :6123-6129