Faculty

 Immunopathogenesis of Helicobacter pylori

     Dr. Eaton is a board-certified veterinary pathologist (diplomate of the American College of Veterinary Pathologists) with research interests in bacterial pathogens of the gastrointestinal tract, host-pathogen interactions, and intestinal immunity.  Her laboratory has three main research directions.

Helicobacter pylori

     H. pylori is a bacterial pathogen of humans that causes gastritis, peptic ulcer, and gastric cancer.  It is found naturally only in the human stomach, and is now thought to cause disease via induction of an exuberant mucosal Th-1 biased immune response.  Dr. Eaton has been studying H. pylori for more than 20 years and has used several animal models including germ-free piglets, gerbils, and mice to investigate a variety of bacterial colonization and virulence factors as well as aspects of host immune response.  We currently use an adoptive transfer mouse model in which T cells from immunocompetent mice are adoptively transferred into H. pylori-infected immunodeficient mice.   Non-transferred immunodeficient mice support large numbers of bacteria in their stomachs with no gastritis, adaptive immune response, or pathologic lesions.  Mice that receive immunocompetent T cells, however, develop rapidly progressive severe gastritis.  This model allows us to investigate separately the 1) direct effect of bacteria upon gastric epithelium in non-transferred mice, and 2) the effect of specific immune cells and cytokines in recipient mice.  The current focus of the laboratory is the role of bacterial LPS O-antigen in and the contribution of Th-1 and Th-17 cells and cytokines to induction of the host immune response.

Enterohemorrhagic E. coli (EHEC)

     EHEC are Shiga-toxin producing pathogenic E. coli most often of the O157 serotype.  They are food-borne pathogens of humans, and cause severe hemorrhagic colitis and sometimes hemolytic-uremic syndrome (HUS), a life-threatening triad of acute renal failure, hemolysis, and thrombocytopenia.  The Eaton laboratory uses a germ-free mouse model to study bacterial factors that promote renal disease and to examine the differential expression of bacterial genes in vivo.

Germ-free and gnotobiotic mice

     In addition to H. pylori and EHEC studies, Dr. Eaton has established a germ-free and gnotobiotic mouse facility at the University of Michigan.  This multi-user facility derives, produces, and maintains several strains of germ-free and gnotobiotic mice for investigator use. Germ-free mice are completely free of exogenous bacterial, fungal, and viral microorganisms. They can be bred and maintained free of microbiota indefinitely in soft-sided bubble-type isolators, or for short periods in sterile microisolator cages in a laminar flow hood.  These mice are ideal for the study of host pathogen interactions in a controlled environment, and for study of the roles of normal microbiota or their absence on host physiology and disease.  Mice in our facility are currently used for the study of infectious diseases such as EHEC, Campylobacter jejuni, and Vibrio cholerae, and the role of enteric microbiota in gastric and colon cancer.  Gnotobiotic mice are germ-free mice that have been deliberately colonized with one or more bacterial species and maintained free of unwanted microbiota in sterile bubble isolators.  These mice are used in infectious disease studies and studies of the interaction between host and microbiome.

PubMed Listing for Dr. Eaton.

Selected Publications:

    Eaton, K.A., et al., A reproducible scoring system for quantification of histologic lesions of inflammatory disease in mouse gastric epithelium. Comp Med, 2007. 57(1): p. 57-65.

     Lopez-Diaz, L., et al., Parietal cell hyperstimulation and autoimmune gastritis in cholera toxin transgenic mice. Am J Physiol Gastrointest Liver Physiol, 2006. 290(5): p. G970-9.

    Kao, J.Y., et al., Helicobacter pylori-secreted factors inhibit dendritic cell IL-12 secretion: a mechanism of ineffective host defense. Am J Physiol Gastrointest Liver Physiol, 2006. 291(1): p. G73-81.

    Eaton, K.A., et al., Role of transcription factor T-bet expression by CD4+ cells in gastritis due to Helicobacter pylori in mice. Infect Immun, 2006. 74(8): p. 4673-84.

     Zavros, Y., et al., Chronic gastritis in the hypochlorhydric gastrin-deficient mouse progresses to adenocarcinoma. Oncogene, 2005. 24(14): p. 2354-66.

    Krakowka, S., et al., Isolation and preliminary characterization of a novel Helicobacter species from swine. Am J Vet Res, 2005. 66(6): p. 938-44.

    Eaton, K.A., et al., Helicobacter pylori with a truncated lipopolysaccharide O chain fails to induce gastritis in SCID mice injected with splenocytes from wild-type C57BL/6J mice. Infect Immun, 2004. 72(7): p. 3925-31.

     Dailidiene, D., et al., Helicobacter acinonychis: genetic and rodent infection studies of a Helicobacter pylori-like gastric pathogen of cheetahs and other big cats. J Bacteriol, 2004. 186(2): p. 356-65.

    Wanken, A.E., T. Conway, and K.A. Eaton, The Entner-Doudoroff pathway has little effect on Helicobacter pylori colonization of mice. Infect Immun, 2003. 71(5): p. 2920-3.

    Peterson, R.A., 2nd, T. Hoepf, and K.A. Eaton, Adoptive transfer of splenocytes in SCID mice implicates CD4+ T cells in apoptosis and epithelial proliferation associated with Helicobacter pylori-induced gastritis. Comp Med, 2003. 53(5): p. 498-509.

    Eaton, K.A., et al., In vivo complementation of ureB restores the ability of Helicobacter pylori to colonize. Infect Immun, 2002. 70(2): p. 771-8.

     Joyce, E.A., et al., Differential gene expression from two transcriptional units in the cag pathogenicity island of Helicobacter pylori. Infect Immun, 2001. 69(7): p. 4202-9.

    Eaton, K.A. and M.E. Mefford, Cure of Helicobacter pylori infection and resolution of gastritis by adoptive transfer of splenocytes in mice. Infect Immun, 2001. 69(2): p. 1025-31.

    Eaton, K.A., M. Mefford, and T. Thevenot, The role of T cell subsets and cytokines in the pathogenesis of Helicobacter pylori gastritis in mice. J Immunol, 2001. 166(12): p. 7456-61.