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Infection and Immunity, September 2005, p. 5468-5481, Vol. 73, No. 9
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.9.5468-5481.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Concurrent Infection with an Intestinal Helminth Parasite Impairs Host Resistance to Enteric Citrobacter rodentium and Enhances Citrobacter-Induced Colitis in Mice

Chang Gung University and Chang Gung Children's Hospital, Taoyuan, Taiwan,¹ Mucosal Immunology Laboratory, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts²

Received 6 August 2004/ Returned for modification 29 September 2004/ Accepted 8 May 2005

Infections with intestinal helminth and bacterial pathogens, such as enteropathogenic Escherichia coli, continue to be a major global health threat for children. To test the hypothesis that intestinal helminth infection may be a risk factor for enteric bacterial infection, a murine model was established by using the intestinal helminth Heligomosomoides polygyrus. To analyze the modulatory effect of a Th2-inducing helminth on the outcome of enteric bacterium Citrobacter rodentium infection, BALB/c and STAT 6 knockout (KO) mice were infected with H. polygyrus, C. rodentium, or both. We found that only BALB/c mice coinfected with H. polygyrus and C. rodentium displayed a marked morbidity and mortality. The enhanced susceptibility to C. rodentium and intestinal injury of coinfected BALB/c mice were shown to be associated with a significant increase in helminth-driven Th2 responses, mucosally and systemically, and correlated with a significant downregulation of protective gamma interferon and with a dramatic upregulation of the proinflammatory tumor necrosis factor alpha response. In addition, C. rodentium-associated colonic pathology in coinfected BALB/c mice was significantly enhanced, whereas bacterial burden was increased and clearance was delayed. In contrast, coinfection in STAT 6 KO mice failed to promote C. rodentium infection or to induce a more severe intestinal inflammation and tissue injury, demonstrating a mechanism by which helminth influences the development of host protective immunity and susceptibility to bacterial infections. We conclude that H. polygyrus coinfection can promote C. rodentium-associated disease and colitis through a STAT 6-mediated immune mechanism.

Editor: J. F. Urban, Jr.

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