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Infection and Immunity, February 2003, p. 910-921, Vol. 71, No. 2
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.2.910-921.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Vaccine-Induced Reduction of Helicobacter pylori Colonization in Mice Is Interleukin-12 Dependent but Gamma Interferon and Inducible Nitric Oxide Synthase Independent

Christine A. Garhart,1* Frederick P. Heinzel,2 Steven J. Czinn,1,3 and John G. Nedrud1

Departments of Pathology,1 Geographic Medicine,2 Pediatrics, Case Western Reserve University, Cleveland, Ohio 441063

Received 22 July 2002/ Returned for modification 8 October 2002/ Accepted 1 November 2002

Previous studies with mice have shown that major histocompatibility complex class II (MHC-II) is required for protection from Helicobacter pylori, while MHC-I and antibodies are not. Thus, CD4+ T cells are presumed to play an essential role in protective immunity via secretion of cytokines. To determine which cytokines are associated with a reduction of bacterial load in immunized mice, gastric cytokine expression was examined by semiquantitative reverse transcription-PCR in protected (defined as >=2-log-unit decrease in bacterial load) and unprotected mice 4 weeks after challenge. Elevated levels of mRNA for interleukin-12p40 (IL-12p40), gamma interferon (IFN-{gamma}), tumor necrosis factor alpha, and inducible nitric oxide synthase (iNOS) were associated with protection in immunized-challenged (I/C) mice, but Th2 cytokine (IL-4, IL-5, IL-10, and IL-13) and chemokine (KC, MIP-2, and MCP-1) expression was not associated with protection. Despite the association of IFN-{gamma} and iNOS message with protection, I/C mice genetically lacking either of these products were able to reduce the bacterial load as well as the wild-type I/C controls. The I/C mice lacking IL-12p40 were not protected compared to unimmunized-challenged mice. All I/C groups developed gastritis. We conclude that neither IFN-{gamma} nor iNOS is essential for vaccine-induced protection from H. pylori infection. The p40 subunit of IL-12, which is a component of both IL-12 and IL-23, is necessary for protection in immunized mice. These findings suggest a novel IFN-{gamma}-independent function of IL-12p40 in effective mucosal immunization against H. pylori.

* Corresponding author. Mailing address: Department of Pathology, Case Western Reserve University, Biomedical Research Building, Room 901, 10900 Euclid Ave., Cleveland, OH 44106-4943. Phone: (216) 368-1274. Fax: (216) 368-1357. E-mail: cag12{at}po.cwru.edu.

Editor: D. L. Burns

Infection and Immunity, February 2003, p. 910-921, Vol. 71, No. 2
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.2.910-921.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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