This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lemke, L. B.
Right arrow Articles by Fox, J. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lemke, L. B.
Right arrow Articles by Fox, J. G.

 Previous Article  |  Next Article 

Infection and Immunity, May 2009, p. 2147-2158, Vol. 77, No. 5
0019-9567/09/$08.00+0     doi:10.1128/IAI.01395-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Concurrent Helicobacter bilis Infection in C57BL/6 Mice Attenuates Proinflammatory H. pylori-Induced Gastric Pathology{triangledown}

Laura B. Lemke,1,2,{dagger},{ddagger} Zhongming Ge,1,{dagger} Mark T. Whary,1 Yan Feng,1 Arlin B. Rogers,1 Sureshkumar Muthupalani,1 and James G. Fox1,2*

Division of Comparative Medicine, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Bldg. 16-825, Cambridge, Massachusetts 02139,1 Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Bldg. 56-651, Cambridge, Massachusetts 021392

Received 13 November 2008/ Returned for modification 16 December 2008/ Accepted 4 February 2009

Because coinfections can alter helicobacter gastritis, we investigated whether enterohepatic Helicobacter bilis modulates Helicobacter pylori gastritis in C57BL/6 mice. Thirty mice per group were sham dosed, H. bilis or H. pylori infected, or H. bilis infected followed in 2 weeks by H. pylori and then evaluated at 6 and 11 months postinfection (mpi) for gastritis and premalignant lesions. Compared to H. pylori-infected mice, H. bilis/H. pylori-infected mice at 6 and 11 mpi had less severe gastritis, atrophy, mucous metaplasia and hyperplasia (P < 0.01) and, additionally, at 11 mpi, less severe intestinal metaplasia and dysplasia (P < 0.05). H. bilis/H. pylori-infected mice at 11 mpi exhibited less Ki67 labeling of proliferating epithelial cells, reduced numbers of FoxP3+ T-regulatory (TREG) cells, and lower FoxP3+ mRNA levels than did H. pylori-infected mice (P < 0.05). Proinflammatory interleukin-1β (IL-1β), gamma interferon, and tumor necrosis factor alpha mRNA levels were attenuated in H. bilis/H. pylori-infected mice at 6 and 11 mpi (P < 0.01), although anti-inflammatory IL-10, IL-13, and transforming growth factor β1 mRNA levels were not consistently impacted by H. bilis coinfection. Decreased pathology in H. bilis/H. pylori-infected mice correlated with higher gastric H. pylori colonization at 6 mpi (P < 0.001) and lower Th1-associated immunoglobulin G2c responses to H. pylori at 6 and 10 mpi (P < 0.05). We hypothesized that reduced pathology in H. bilis/H. pylori-infected mice was due to H. bilis-primed TREG cells in the lower bowel that migrated to the gastric compartment and inhibited Th1 responses to subsequent H. pylori infection. Thus, H. pylori-induced gastric lesions may vary in mouse models of unknown enteric helicobacter infection status and, importantly, variable sequelae to human H. pylori infection, particularly in developing countries, may occur where coinfection with lower bowel helicobacters and H. pylori may be common.

* Corresponding author. Mailing address: Division of Comparative Medicine, Massachusetts Institute of Technology, 77 Massachusetts Ave., Bldg. 16-825, Cambridge, MA 02139. Phone: (617) 253-1757. Fax: (617) 258-5708. E-mail: jgfox{at}mit.edu

{triangledown} Published ahead of print on 17 February 2009.

Editor: A. J. Bäumler

{dagger} L.B.L. and Z.G. contributed equally to this study.

{ddagger} Present address: Animal Resources Center, University of Texas at Austin, University Station, A2500, Austin, TX 78712-0136.

Infection and Immunity, May 2009, p. 2147-2158, Vol. 77, No. 5
0019-9567/09/$08.00+0     doi:10.1128/IAI.01395-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»